Dr. E.J. Chichilnisky: How the Brain Works, Curing Blindness & How to Navigate a Career Path
welcome to the huberman Lab podcast
where we discuss science and
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[Music]
life I'm Andrew huberman and I'm a
professor of neurobiology and
Opthalmology at Stanford School of
Medicine my guest today is Dr EJ chelski
Dr EJ chelski is a professor of
neurosurgery Opthalmology and
Neuroscience at Stanford University he
is one of the world's leading
researchers trying to understand how we
see the world around us that is how
visual perception occurs and then
applying that information directly to
the design of neural prosthesis
literally robotic eyes that can allow
blind people to see once again today's
discussion is a very important one for
anyone who wants to understand how their
brain works indeed EJ spells out in very
clear terms exactly how the world around
us is encoded by the neurons the nerve
cells within our brain in order to
create these elaborate visual images
that we essentially see within our minds
and with that understanding he explains
how that can be applied to engineer
specific robotic Ai and machine learning
devices that can allow human brains not
only to see once again in the blind but
also to perceive things that typical
human brains can't and indeed for memory
to be enhanced and for cognition to be
enhanced this is the direction that
Neuroscience is going and in the course
of today's discussion we have the
opportunity to learn from the world
World expert in these topics where the
science is now and where it is headed
during today's discussion we also get
heavily into the topic of how to select
one's professional and personal path and
indeed you'll learn from Dr chelski that
he has a somewhat unusual path both into
science and through science so for those
of you that believe that everyone that's
highly accomplished in their career
always knew exactly what they wanted to
do at every stage you will soon learn
that that is absolutely not the case
with EJ he described
wandering through three different
graduate programs taking several years
off from school in order to dance Yes
you heard that correctly to dance and
how that wandering and indeed dancing
helped him decide exactly what he wanted
to do with his professional life and
exactly what specific problems to try
and Tackle in the realm of Neuroscience
and medicine it's a discussion that I'm
certain that everybody scientist or no
young or old can benefit from and can
apply the specific tools that EJ
describes in their own life and Pursuits
before we begin I'd like to emphasize
that this podcast is separate from my
teaching and research roles at Stanford
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huberman and now for my discussion with
Dr EJ
chelski Dr EJ chelski welcome good to
see you for the audience we are friends
we go way back EJ has been a few years
or more ahead of me in the science game
and the best way to describe you and
your work EJ is you're an astronaut you
go places no one else has been willing
to go before he developed new
technologies in order to do that all
with the Bold mission of trying to
understand how the nervous system which
of course includes the brain works and
how to make it better with engineering
so today we are going to get into all of
that but just to start off and get
everybody on the same page maybe we
could just take a moment and talk about
the brain and nervous system and you
know what it consists of that allows to
do all the sorts of things that we're
going to get into like see things in our
environment and respond to those things
in our environment so at risk of
throwing too much at you right out the
gate what's your one to five minute
version of how the brain
works oh I don't have a one to five
minute version of how the brain works
but I can tell you how I think uh vision
is initiated in the brain and
um you and I go back a long way so we
have a lot of common understanding about
this but I'll narrate it from scratch if
if that makes
sense um so vision is initiated in the
retina uh of the eye which is a sheet
neural tissue at the rear of the eye
that captures the light that is incident
on the eye that comes in through the
through the eye transforms that light
into electrical signals processes those
electrical signals in interesting ways
and changes them up and then sends that
visual information to the brain where it
is used to bring about our sense of
vision and uh you you asked me about the
1 to five minute version how the brain
works I don't know but I do know that
the brain receives all these patterns of
electrical activity coming out of these
nerve cells and the retina and somehow
assembles that into our visual
experience whether that be responding to
things coming at us or our circadian
rhythm
that that govern our sleep and behavior
or identifying objects for prey or
avoiding Predators or appreciating
Beauty and what we know is that the
brain receives a fantastically complex
set of signals from the retina and puts
that all together into our visual
experience and we are very visual
creatures obviously so I think that's a
big part of how the brain works because
so much of what we do revolves around
vision revolves around how the brain
puts together these signals coming out
of the retina and I would love to
understand how that works at the moment
I don't uh and what we're trying to do
is get a really complete understanding
of how that begins in the retina and
then how we can restore it and those who
have lost
sight why focus on this issue in the
retina this thin set of layers of
neurons that line the back of the eye
what why why explore there I mean
obviously there are centers within the
brain that of course contain neurons
nerve cells that are involved in Vision
if one wants to understand visual
perception and I agree by the way that
visual perception is one of the most
dominant forces in the quality and
experience of our
life why focus on the retina why not
focus on the visual cortex or the visual
thalmus I me what's so special about the
retina well we have to focus on all of
it because understanding the retina
won't give us a full understanding of
how all this works obviously and if you
don't have your visual cortex and visual
Thalamus you won't see but if you don't
have your retina you also won't see you
won't even have a chance to see so I
focus on the retina because um I enjoy
the possibility that we can really
understand a piece of the nervous system
in my lifetime in our lifetimes we can
understand it so well that we can build
it replace it restore its function
that's farther off in this in the
central regions of the brain it's going
to be quite a bit harder um I find
satisfaction in really understanding
something so well that I can write down
in a mathematical formula what it's
doing that I can test my hypothesis up
and down and yes we really get how this
little machine works and that I can
engineer devices to replace the function
of that circuit when it's lost that to
me is just deeply satisfying but there
also has is a really fundamental role
for people who want to go and do more
exploratory work in the visual brain as
you mentioned in the visual cortex and
the phalus and other places because
ultimately those retinal signals won't
lead to anything if those areas aren't
putting it all together to govern our
perception and our ultimately our
Behavior so let's talk about the retina
in its full Beauty and
detail three layers of cells line the
back of the eye like a pie
crust somehow take light that comes into
the eye lens focuses that light if it
doesn't do that well we put lenses in
front of our eyes such as contact lenses
or
spectacles and somehow takes that light
and transforms it as you said into
neural signals and processes that within
the retina so let's take a deep dive
into the retina and do so with the
understanding at least my understanding
is that
in part thanks to your work and the work
of others this is perhaps the best
understood piece of the brain yes I
think it's a solid argument that it's
the best understood piece of the brain
and uh we'll turn back to that in a
minute so um the retina begins with a
sheet of cells called the photo receptor
cells that are highly specialized these
are cells that essentially don't exist
anywhere else in the brain and what they
do is transform light energy into
electrical signals in neurons very
specialized very uh demanding cells they
require a lot of Maintenance and they
die relatively easily which is what
gives rise to some some of the forms of
blindness those are the you might call
them pixel detectors they're tiny cells
called photo receptors that each one
captures light from a particular
location in the
world that sheet of cells has done that
initial transduction process where light
is converted into neural signals that
the brain can then begin to work with
the second layer is responsible
for processing adjusting changing mixing
and matching uh comparing signals and
different neurons many complex
operations that we're still trying to
understand and consists of dozens of
distinct cell types that extract
features if you will of the visual World
from the elementary pixels represented
in the photo receptor cells so that
second layer is receiving the input from
that sheet of photo receptors and
picking stuff out of
it the third layer of cells is the
so-called retinol gangan cells that's
the only uh term that I'd like to
probably will come up repeatedly in this
conversation uh so for your for your
viewers and listeners um these retinol
ganglin cells are the ones who are
responsible for taking the signals that
are there in the retina and sending them
to the brain so that the process of
vision can begin they are the The
Messengers if you will from the retina
to the brain the retinal ganglin cells
and there are about 20 different types
in humans um are again feature
extractors they pick out different bits
and pieces of the visual scene and send
interesting stuff to the brain trying to
leave out the uninteresting stuff and
the 20 or so cell types all pick out
different types of information from the
visual scene you can sort of think of
them as Photoshop filters each cell type
in the retina um again about 20
different gangin cell types each type
represents the full scene the entire
visual world but picks out different
features such as some cells pick out
spatial detail tiny little Points of
Light almost some cells pick out and
Signal information about things that are
moving in the visual World some cells
pick out information that's been
captured about different wavelengths
from the photo receptor cells and there
thereby giving us our sensations of
color and probably more things in those
20 different gangin cell types that we
don't fully
understand the result then is that the
retina has this sort of a representation
of the visual world but it has 20
different representations not one it's
not one picture that comes out of the
retina and gets sent to the brain no no
no it's 20 different pictures and you
can think of maybe as 20 different
photoshopped pictures but one of them
has the edges highlighted one of them
has the colors highlighted one of them
has movement uh encoded in it and these
somehow these filters send the
information to many different targets in
the brain and our brain puts it off Al
together and then we have a cohesive
sense of the visual World which is the
remarkable feature that we really don't
understand
amazing is it fair for those that don't
work with Photoshop to think about these
um different Photoshop filters perhaps
as like different movies of the visual
world one movie contains the outlines of
objects and people and things another
movie is showing the motion of blobs in
the environment meaning whatever is
moving environment is kind of just
represented as blobs another movie is
just the color in the environment
another and then all of those what I'm
calling movies are sent into the brain
and then the brain somehow combines
those in ways that allow us to see each
other and see cars and objects and
recognize faces is that is that one way
to think about that that's exactly how I
think about it maybe it's a better way
to say it no I I I like the Photoshop
filter uh analogy I just for those that
don't work with Photoshop um you know I
I just think that the movie analogy
might might be a decent alternative how
the retina works is an example we think
of how all sensory systems work there's
an initial representation in a
specialized cell type that is it is that
is responsible for and capable of
extracting physical features from the
world and then neural circuits in the
brain use that information in different
ways to grab stuff out of the visual
world in the auditory system there's the
the sound world is represented also in
specialized cells that capture sound
energy and transduce that into neural
signals and then subsequent p uh stages
of processing in the auditory system
pick out different features of our
auditory world like the frequency how
high or how low a tone is right the
direction it's coming from right the
movement of it uh how loud it is
different features are extracted so the
we think the visual system is just an
example of how the external world is
represented in our brain and of course
in some sense a a philosophical approach
to the brain is really saying well
there's the sensory world and then
there's the actions we take and there's
almost nothing else that we really know
other than those two things how the
sensory world comes in and then finally
it results in our action that's what our
brain is about because vision is so
important for people I find it
absolutely compelling and fascinating I
mean as an example as you know well many
people study rodents
uh to understand how different aspects
of the brain work and um you know
rodents are interesting animals and do
all sorts of really cool things but they
interact with the world differently than
we do they in in a lot of ways they
sense by smelling they they identify
objects by smelling and they navigate
with their whiskers in to a large extent
we don't do any of that you don't
navigate with your whiskers at least I
don't think you do you don't recognize
me when I walk in the room by my smell
no you use for all that and we humans
use Vision so it's a really fundamental
aspect of who we are as biological
creatures I wonder if just for sake of
entertainment uh we could think about
how the human retina and therefore
Vision in our species differs a little
bit from some extreme examples of vision
in other species not to make this a
comparative um or Zoological um
exploration but just to really
illustrate the fact that the specific
cell types within our
retinas create a visual representation
of the outside world that can be and
often is very different from that of
other species um for instance or at
least my understanding is that the
mantis shrimp sees I don't know 60 to
100 different variations of each color
that we are essentially blind to because
their photoreceptors can detect very
subtle differences in red for instance
long wavelengths of light what most
people refer to as red um pit vipers
cons sense heat
emissions essentially with their eyes
but also other organs um and on and on
you know it I raise this because I think
the the human neuro retina is such an
incredible example of extracting
features from the visual world that then
we recreate but I think it's also worth
reminding everyone and ourselves that
it's not a complete representation of
what's out there like there's a lot in
light that we don't see because our
neuro retina just can't turn it into
electrical signals right you want to
give some examples of what we can't see
and if any um particular examples from
the Animal Kingdom Delight you feel free
to throw those out well one thing you
mentioned color um we experience a rich
sensation of color when we look at the
world and say wow I see all these colors
that's immediate
and that's just how we talk about it but
in fact we have very little information
about color color is a very
high-dimensional complex thing or
wavelength I should say wavelength
information really is about how much
energy there is in the light around us
at different wavelengths we only have
three sort of snapshots of that in our
retinas with the three different types
of photo receptor cells that are
sensitive to different wavelength
different bands of the wavelength
Spectrum three is not a lot as you just
said other creatures have many more ways
of capturing wavelength information and
one way you can verify for yourself that
we just have three is to realize that if
you look at your TV there are only three
primaries on your TV there's a red
there's a green and there's a blue
that's it and from those three primaries
the entire richness of the experience on
your TV set is uh composed so with just
those three things you basically are
able to create any human visual
sensation well the mantis shrimp would
be like that's nothing there's so much
more stuff out there that's not
represented on this TV if you could
speak to the mantis shrimp another thing
we we maybe don't see another example of
a difference in the animal kingdom is so
um again taking rodents as an example
one of the one of the things rodents
have to do is to not be hunted by birds
that are coming down toward them
and so it it appears that there are
cells in the retina that
are seem to be quite sensitive to what
to uh looming to something dark that's
getting bigger uh like a shadow coming
from a bird coming down at you we don't
know for sure that this is exactly what
causes animals to avoid being eaten by
birds but there's there's interesting
evidence in that direction that's not
really a big thing for us for humans as
far as I know we're not typically hunted
by huge birds so that's not a thing we
need and I think that's that's where
comes back to where you were headed if I
understand right um which is we occupy
different biological niches we and the
Manta shrimp and the rodents and our
visual systems reflect that we have
different stuff that we're looking for
in our visual environment than other
creatures are and so our eyes are
different and that's one of the reasons
that we emphasize work on the human
retina um as opposed to other certain
other animal species that would be less
clearly relevant to the visual
experience you and I have so let's talk
about these incredible experiments that
your laboratory has been doing for
several decades now I've had the uh
privilege of sitting in on some of these
experiments and they are very involved
um to say the least if you could just
walk us through one of these experiments
I think the audience would appreciate
understanding what goes into quote
unquote trying to understand what's
going on in the electrical activity of
these specific retinal cell types the
retinal gangling cells in particular um
you know what does this look like you
know you're in your laboratory at
Stanford and you get a phone call
someone says I got a retina what happens
next we scramble like crazy we drop
everything we're doing cancel all our
appointments and get ourselves ready for
48 hours of non-stop work down in the
lab getting as much data as we possibly
can from the retina the most exciting
example of what you just said is when we
get a human retina when for example
there's a a donor who has died and the
retina is available for research we jump
at that opportunity how soon after uh
the person is deceased do you need to
get the eye Globe the eyeball in order
to get the retina in a condition that
would allow you to record electrical
signals from it a few minutes just
you're waiting in the hospital um typic
the way we typically get these eyes is
from brain dead individuals so people
who are legally and medically dead but
they're hearts are still pumping and
therefore their retinas are still alive
and functioning when when those
individuals uh are used their the bodies
of those individuals are used for organ
donations we can benefit from that organ
donation setup that organ distribution
centers do to save many people's lives
and also to promote research so we
sometimes get those retinas and that
begins the experiment for us um I'm
gonna ask for a few more details here
just to put the picture in people's
minds and not to be gruesome I just
really want people to understand what's
involved here so you'll get a call we've
got a a patient who is soon to be
deceased um they've consented to giving
their eye Globes their eyeballs for
research so that you can study the human
retina y um is it you who goes over and
takes the eyes out does somebody do that
or hand them to you in a bucket of ice
I'm sorry if I'm making people queasy at
all but th this is folks how uh one goes
about trying to understand understand
how the human brain works absolutely and
this is also how you go about donating
your heart so that you can save somebody
else's life who needs a heart transplant
the same incredible organizations that
do the harvesting of the tissue for us
their primary goal is to do that for
organ donations to save lives they save
lives every day these people are
incredible donor Network West is one of
those organizations the one that we work
with um they're really amazing um so
their technicians or a retinal surgeon
will take the eye out give it to myself
or some somebody from my lab who will
bring it back to the lab and we have a
way to keep the eye alive and
functioning just the eye by itself is
this always at Stanford or do you
sometimes travel elsewhere local
hospitals up to an hour away so then you
drive them back we drive them back it's
the retina Express and when when we're
bringing back the retin Express it's uh
again it's all hands on deck in our lab
we are scrambling setting up all of our
equipment getting everything ready
you've been at these experiments they're
intense and they really are really are
48 hour marathons of incredible activity
by really dedicated individuals so um we
we might get those eyes sometimes we get
them at 2 in the morning that's common
and from that to in the morning time um
Begins the experiment so we bring the
eyes back we open them up and we we have
access to the rear of the eye which is
what the where the retina is it's a thin
sheet of neural tissue at the back part
of the eye we hemis the eye cut it in
half so that we can see the back it's
like half of a glow if you will and then
we put in relaxing cuts and lay it out
flat so we can see what we're working
with then we take little segments of
retina out in the subsequent 48 Hours
cut them out maybe a 3X3 millimeter
piece of the retina a little chunk of
retinal tissue and bring it into an
electrophysiology recording and
stimulation apparatus that allow allows
us to interact with it and we do two
types of experiments with that so this
electrophysiological recording and
stimulation apparatus is very custom
built by our physics collaborator who
have developed high-end equipment it
allows us to record and stimulate
through 512 channels simultaneously at
very high density this is pretty
high-end stuff in terms of uh technology
for interrogating and manipulating the
electrical signals in the retina that's
what we specialize in in my lab could I
just ask a question about this device um
I've seen it before uh it's very small
as you mentioned your recording from a
few millimet square of the of the retina
um from this recently deceased patient
um it looks a little bit like a bed of
nails right like tiny little microwires
all arranged very Clos to one another
you got the retina laying down on top of
it and that bed of nails can extract
meaning record the electrical signals
that are coming out of the retinal
gangion cells that's right and the
retina is still alive so you are in a
position to shine light on it and
essentially um make it behave um um in
the same way it would if it were still
lining the back of a healthy alive
person that is the beauty of these
experiments so because we can keep the
retina alive and happy and because the
retinal ganglin cells the cells that are
the ones that message the visual
information to the brain are on the
surface we can put them right next to
the electrodes and we can record their
electrical activity in other words we
record the signal that those cells would
have sent to the brain if they were
still in the living person and at the
same time as you said we can focus an
image that we create on a computer
display onto the retina so we're
treating the retina if you will as a
little electronic circuit which it
almost is honestly delivering light to
the photo receptor cells so that they
are electrically excited and then
recording the electrical activity that
the retina is sending out if you will
that allows us to study how the retina
Works
normally what we also do with that same
electrical apparatus is turn around and
pass current through those electrodes in
order to see if we can activate those
ganglin cells directly with no light
just electrodes why do we do that we do
that because it allows us to design
future methods of restoring Vision by
electrical stimulation of the retina
which we'll probably talk about in a few
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huberman let's take this moment to talk
a little bit about cell types so um you
mentioned there are about 20 different
types of these retinal gangling cells
what we may refer to in brief as r gc's
so retinal gangling cells rgc's same
thing
and as you mentioned these cover the
entire retina so that if each cell type
is extracting a different set of
features from the visual World motion
color specific colors
Etc that essentially no location in the
world around us fails to be represented
by these cells put differently these
cells are looking everywhere um each
cell
cell type is looking everywhere um so
that if movement occurs in any region of
our visual world we are in a position to
detect it um but maybe we could talk a
little bit about cell types cell types
is such an important theme in the field
of Neuroscience and indeed in all of
biology but it's actually not something
we have talked about very much on this
podcast before either in Solo episodes
or in guest episodes um I don't have any
specific reason for that we've talked
about brain areas prefrontal cortex
basil ganglia anterior mingal cortex and
on and on we' talked about neural
circuits but we've never really talked
about cell types so the gangan cells as
other you let me down no talking about
cell types well but that's why you're
here that's why I'm here that's why
you're here um tell us about cell types
how do you figure
out if you have a cell type how do you
know if it's a cell type or you know is
it the shape is it how it responds um
how do you know if you have a cell type
what what's this about and I want to
just um put in the back of this question
um or rather in the back of people's
minds that um this issue of cell types
is not just an issue pertinent to the
retina this is an issue that is critical
to understanding how the brain works
absolutely it's critical to understand
Consciousness I know a lot of people
like what is consciousness right we're
not going there just yet but uh what are
cell types how do you determine if you
have a cell type and why is this so
important to understanding how the brain
works yeah I mean as as you said as as
far as we understand every single brain
circuit is full of very distinct cell
types those cell types are distinguished
by their genetic expression their shapes
and sizes which other cells they do
contact and which cells they don't
contact where they send their
information to in other parts of the
brain and what they represent and as far
as we know this is true throughout the
brain and it's true in the retina the
different gangling cell types retinal
ganglin cell types about 20 of them Each
of which is looking at the whole visual
scene extracts different stuff this cell
type one extracts one thing cell type
two extracts something else but they all
represent the entire visual scene but
those cell types we know from lots of
beautiful work work that you're closely
connected to and some of which you've
done um those cell types have different
morphology different shapes and sizes
different patterns of gene expression
different targets in the brain they send
their outputs to different places in the
brain so really to study the retina
without understanding cell types you're
kind of lost right away you have to know
what's going on with the cell types
otherwise you can't make sense of this
retinol signal the way we we identify
them in two ways and they're different
for different purposes the the basic way
we identify the different cell types is
their function because we study their
function we study how they respond to
light images and we can clearly separate
them out and in fact it's it's a simple
thing to say but it's really true our
512 electrod technology which you've
seen in our lab and stuff that developed
with collaborators um about 20 years ago
um was crucial for this because with
that 512 electrode technology we could
see many cells of each type and we could
clearly parse them apart from one
another whereas previous studies working
on one cell at a time had great
difficulty doing that so with our
technology with 512 electrodes we record
hundreds of cells simultaneously we say
oh there's 20 of these there are 50 of
those there's 26 of those and here they
are and we can just set them in
different bins and say okay this is
what's present in this retina just what
the information is they're
extracting there's another purpose again
referring forward to the
neuroengineering aspect we need to
identify the cell types not just based
on what visual information they carry
but based on their electrical features
properties electrical properties of the
cells cells as you know neurons are
electrical cells they fundamentally
receive and transmit electrical
information and the way that they do
that has a distinctive electrical
signature that turns out to be super
important for developing devices to to
restore
Vision could you explain how you
determine what a given cell type does
its electrical properties um let's just
draw a mental image for people uh the
retina's taken out of this deceased
individual put down on this bed of nails
of electrodes those electrodes can
detect electrical signals within the
gangling cells you are able to shine
light onto the retina and see how the
retinal gangling cells respond meaning
what electrical signals they would
transmit to the brain if they were still
connected to a brain they're not
connected to a brain in the experiment
they're sitting there they're trying but
they're
trying I could imagine playing those
cells a movie of I don't know a
checkerboard going where every um Square
on the checkerboard goes from white to
black to gray could do that I could um
play a
cartoon I could um show it uh this
year's Academy Award winner for best
picture like how do you decide what to
show the retina this is a human being's
retina after all uh presumably it looked
at things that are relevant to human
beings until that person died but how do
you determine cell type electrical
signals if you don't know what specific
things to show it I mean you're going to
show it I don't know Disney movies like
what what do you show
it
so what we shown now reflects the fact
that we've built up a lot of information
and our work stands on the shoulders of
many scientists who have studied the
retina for decades to figure out what
different cell types respond to and um
we know that certain cell types respond
primarily to increments of light when
light gets brighter than it was so a
change from a certain brightness to a
higher brightness this particular cell
type fires another cell type fires or
send spikes to the brain when it gets
darker some cell types uh respond
primarily to large Targets in the visual
World other cell types respond better to
small Targets in the visual
World some cell types respond to
different wavelengths of light that we
can identify there exist certain cell
types that are still poorly understood
that respond to movement so we can
tailor visual stimuli to types that we
kind of already know about because of
much preceding
research that's not actually how we do
it in our experiments for the most part
instead we use a very unbiased
flickering checkerboard pattern as it
turns out which is a really efficient
unbiased way to sample many cells
simultaneously so that in a half hour of
electrical recording from a retina we
can figure out what all the 512 or so
cells are that we're recording and know
all of their types and the way we do
that is to play essentially random
garbage TV snow Type image to the retina
for a period of time and determine which
bits of of brightening or darkening or
movement or whatever in that random
garbage activated this particular cell
by looking AC at average across the half
hour recording and saying oh it looks
like this cell was always firing when it
became bright in this region of the
screen that must be an on Cell sensitive
to light in this region of the screen
and so on so we have sophisticated
efficient ways of doing it but it all
comes back to these basic things about
what features in the visual World tend
to cause a given cell to send a signal
to the bra yeah that makes a lot of
sense so you take essentially what you
called random garbage um snow white
black and gray pixels on a
screen yep the retina views that and
then the cells in the retina will
respond every once in a while with an
electrical potential they'll fire as we
say spike it's sometimes called and then
you take sort of a forensic
approach a bit later you look back in
time and you say you know what was the
arrangement of pixels in this random
garbage right before this
cell fired an electrical potential
that's right a spike and then from that
you can reconstruct the preferred
stimulus yeah right the you can say oh
this cell and cells around it seem to
like motion of things going in a
particular direction for instance and um
how do you know know that the cell
doesn't also like a bunch of other stuff
that you
didn't pick up on using
this random garbage yeah two things for
let let me just say for the record we
don't record from these cells that
signal Motion in particular directions
they are an elusive cell type that is
best understood in rodents and other
creatures and not well understood in the
primate as you know although some people
are discovering potential cells of that
type now and have have recently
discovered them okay so let's say cells
that respond
to like spots that are red um you know
that go from dim red to bright red right
yeah so we can go through that colored
TV snow and pick out the cells that
responded to a transition of the kind
you described from darker to lighter or
from Greener to redder or something like
that cells tend to respond to
Transitions in the visual scene rather
than static
imagery um and so we can pick that stuff
out but you asked the question will G is
the TV snow G to capture everything
about what these cells are doing that's
a really important question that I want
to just mention more um quite likely not
that's a scientific instrument it's an
unbiased way to sample a whole bunch of
cells you know first cut look at you
know generally speaking what are they up
to but that doesn't mean we've really
captured their role in natural visual
perception because actually you don't go
through the World perceiving visual snow
you go through the world perceiving
objects and meals and mates and targets
and all these things right so the study
of how the retina responds to more
naturalistic visual stimuli uh in my lab
and in many La other labs around the
world is really get getting off the
ground now and I would say we have
limited understanding um I would say we
know that our simple laboratory
experiments with the TV snow don't
capture the whole story there's more
there're about 20 different cell types
in the retina we have basic
characterizations of seven of them if
you count a certain way um we know that
there are another 15 or so lurking right
behind the curtain that we've started to
sample we don't know what naturalistic
targets they respond to in the visual
life of the animal that's work that's
underway exciting interesting work
because this we know that the r they got
to be there for something one one way to
think of it I'm I'm pretty sure you
think think of it this way too is that
the retina is a highly evolved organ
with a lot of evolutionary pressure for
it to be efficient to have a small optic
nerve sending to the brain it's probably
the case that there's no accidental
stuff sitting around in the retina
that's visal and sending information to
the brain it's probably the case that
this those signals are are all doing
something important for our visual
behavior for our well-being for our
sleep all sorts of stuff and I think and
the field is still trying to figure that
out these these are the big Mysteries I
think that in terms of the retina what
are those signals exactly in all those
different cell types what different
behaviors and aspects of our life do
they
control what is the wildest cell type
you've ever
encountered like what did it do like
what did it respond to that's that's
what I mean when I say wildest um you
know it cells reog gangling cells that
respond to you know increasingly red
portions of the visual scene or
decreasingly green portions of the
visual scene like okay cool that seems
cool like get some you know around the
time of Christmas that that's useful and
it's uh useful on other days of the year
as well but you know given that the
retina is indeed the best understood
piece of the brain and given that you
have 20 cell types 20 isn't 20 million
it's um you know it seems tractable
probably gets understanding it in its
entirety or understanding them in their
entirety excuse me um one would like to
know like what what stuff is are we
paying attention to at the level of the
retina I mean are there like Spiral
sells it like Spiral stuff in the
environment are there sells it like
emojis like what what's going on in
there you spent a lot of time doing this
we do we SP a lot after all you give up
two nights sleep which is kind of
incredible by the way I'll just do a
little uh take a moment here and just
say you know for a guy that's been doing
this for this long with these sleepless
nights um you look pretty good you look
pretty resty
you I tend to go home I go home before
The Graduate students do oh they stay up
they stay up I was used to stay up I
used to stay up until my mid 40s I was I
was in there doing the all nighter type
things got it and um maybe you can help
me figure out my sleep patterns better
yeah yeah we can talk about that this
episode we talk about how to pull all
nighters and still survive done plenty
of those um but yeah like what's yeah
lots at stake here there's a human
retina you know meaning a human gave up
their eyeballs to for this experiment
after they died of
you got many people this these are these
sort of experiments um are very
expensive um a lot of fancy equipment a
lot of salaries to try and figure this
stuff out this is the chief mission of
the national eye institute there's a lot
of tax dollars like this is um in my
opinion as important as the Space
Program probably more important in my
opinion you know restoring Vision to the
blind obviously so what are you finding
in there yeah and and we have the
privilege of being on the front lines of
that funded by the National Institute
and other in tions to be out there
figuring out what's going on in this
human retina I'm with you on that so I
I'll tell you how we go B it these days
there are about seven cell types that we
understand pretty well what they're
doing they're it's not they're not
complicated they just have different
properties color size this kind of thing
temporal properties their timing of
their signals and those seven cell types
we understand pretty well but we're
trying to really nail down the details
why because of neuroengineering for
vision
restoration then there's another I'm
going to say 15 or so and we and the
anatomists the people who study the
shapes and sizes of the cells have long
known that there were more cell types
lurking in the retinal circuitry but
their function has not been known and
because we didn't have many recordings
from them we didn't have electrical
recordings in response to light that
would tell us what they naturally do
we've actually had a breakthrough in the
last few years led by a senior research
in my in my lab named Alexander cing who
has figured out that there's another 15
or so cell types lurking in those
recordings that if we look more
carefully they're there and they have
crazy properties and so the crazy
properties I can tell you about have to
do with the spatial region of the visual
world that they respond to the
well-known cell types that you know and
I know from the textbooks kind of
respond to a circular spot in the visual
world if there's light in this little
circular area they'll fire a spike if
there's no light there they don't care
well okay some cells is not quite
circular some cells respond to the light
that's there and and the difference from
the light that's around it so if it's
brighter than the light that's nearby
then you then you get a big response the
new cell types are more puzzling than
that some of them respond to three or
four blobs in the visual world that's
kind of strange unexpected definitely
unexpected based on the textbooks and
the newest ones are weirder yet some of
them they're their visual response
profiles that is the region of the
visual world that they are sensitive to
light
in almost has a spidery shape almost
like the dendrites of a cell like the
processes of a cell and some of them
have Blobby Light sensitivity they're
sensitive to to light increments here
and decrements there and increments here
and decrements there and some blue light
over here and blue light over here we
don't understand these cells to be clear
the seven that we understand reasonably
well well and not trying to just pin
down and really nail for vision
restoration the sort of first cut at at
cell type specific Vision
restoration those ones don't have these
weird properties they're a little
simpler to understand so we're we're
just but we're just working out all the
details of the timing of the of the
responses and all that these new ones we
don't know what's going on with them so
we're doing experiments those seven cell
types constitute maybe
70% of all the neurons that send visual
information from the eye to the brain so
we think it's a really solid Target for
Vision restoration to work with the
simple
ones and so so when I when I say that I
think that the retina is the best
understood circuit in the nervous system
I'm talking about those seven cell types
which we know a lot about what they do
we really do know a lot it's not done
but we know a lot I'm not talking about
the other 15 cell types which are a
minority of the population but seem to
be doing very strange and surprising
things that are yet to be determined so
there it's a mix we know some really
good stuff and then there's really some
deep Mysteries out there about these
other cell types so we've been talking a
lot about how to understand the signals
that the retina is sending the brain and
I know your lab has done incredible work
in this Arena and figured out a number
of the different signals as you
described some of the features that the
different cell types are extracting just
a moment ago these Blobs of different
colors
Etc what good is this to you know the
everyday person right um What What In
addition to wanting to understand how we
see you know what sort of sorts of
medical applications can this provide in
terms of potentially restoring Vision to
the blind um but perhaps even larger
theme is this notion of neuroengineering
right taking this information and
creating devices that can help us help
our nervous system function better maybe
even function at superphysiological
levels I know there's a lot of interest
in this these days um in part due to
neural link right because elon's out
there front-facing very vocal about his
vision of the no pun intended of you
know chips being implanted in people's
brains that would allow them to be in
conversation with you know 100 people at
the same time just by hearing those
voices in the head maybe filtering
things out so it doesn't sound like a
clamor of a hundred different voices um
perhaps giving people super memory I
mean you know sky the limit no no one
really knows where this is all headed
you're working in what we call a very
strain system where it has specific
properties that you're trying to
understand and once you understand those
you can start to think about real
applications of like what's possible
like could you create a visual system
that um Can extract more color features
from the world that no other human can
see um can you restore um pattern Vision
to somebody who is essentially blind
independent on a cane or a dog or you
know God forbid can't even leave their
house because they can't see anything at
all you know where is this headed what
is the information useful for and
perhaps we should frame that first
within the medical rehabilitative
context of repairing uh or restoring
Vision rather and then get into the more
kind of um uh sci-fi type
neuroengineering stuff absolutely yeah
this this really is my passion these
days turning that corner continuing to
figure out the mysteries in the retina
but also saying wait a second we
actually know quite a lot about this
shouldn't this be the first place that
we can solve problems like restoring
Vision restoring function or augmenting
our function I think it should be the
concept of how to do this is
straightforward and not invented by us
in any way and that is the following one
of the major sources of blindness in uh
the Western world is uh loss of the
photo receptor cells that capture light
macular degeneration and retinitis
Pigmentosa are two well-known ailments
that give rise to to vision loss and the
vision loss is because the cells that
capture light in the first place that we
talked about earlier die off so you're
no longer sensitive to light and then
you're blind the concept is that you may
be able to bypass those early sections
of the retina that capture the light and
process the signals and
instead build an electronic implant that
connects up directly to the retinal
ganglin cells and this electronic
implant would would do the following it
would capture the light using a camera
which is relatively easy it would
process the visual information in a
manner similar to the way that the
retina normally does as similar as
possible and then it would electrically
activate the retinal gangin cells by
passing current and causing the gangin
cells to fire spikes and send those
spikes to the brain and if we do this
really well we can essentially replace
those first two layers of the retina and
piggy back onto the third layer and say
okay we're just jumping right into that
third layer we're going to force those
ganglin cells to send reasonable visual
signals to the brain and then the brain
is going to think it got a natural
visual signal and proceed accordingly
that's the concept this is not our idea
people have had this concept for decades
and some people have even started to
make it work in in human patients and
what I mean by that is implanting
electrodes on the retina stimulating and
causing people who've been profoundly
blind for decades to see visual
sensation blobs and streaks of light in
their visual world that that are
reproducible so so that's happening now
that's happened people who were at once
blind yep are able to see objects are
able to see crude blobs and flashes of
light in ways that allow them to
navigate their world better a little bit
a little bit avoid a coffee table maybe
or at least see a bright window in a
dark wall and be able to point to that
bright window or the bright doorway in a
dark wall something like that so it's a
glass half full half empty story that I
want to turn that I'd like to turn
attention to in this conversation cuz I
I think it's very exciting um yes you
can see stuff by artificially
electrically stimulating the ganglin
cells and you can see stuff that
actually helps you interact with your
world a tiny little bit so great that's
the glass half full the glass half empty
is it's nothing remotely resembling what
we understand as naturalistic Vision
where we see spine spatial detail and
color and objects and can navigate
complex environments and all that stuff
no chance you can't do anything REM
remotely like that you can see that
there's a bright doorway over that way
and turn toward it which is a helpful
step in your Human Experience but
there's a long way to go so the question
is why does this existing technology
fail to give us high quality Vision what
what's needed to give us high quality
vision and this is the piece I'm really
passionate
about it turns out that the the devices
that have been implanted in humans so
far by pioneering bioengineers who did
really hard stuff were were fairly
simple devices that treated the retina
as if it's a camera that is just a grid
of pixels and they put a grid of
electrodes down there and they
stimulated it according to the pixels in
the visual world and thought well
hopefully that will cause the retina to
do the right thing and send a nice
visual piece of visual information to
the brain and initiate Vision
Unfortunately they left the science on
the table and this is actually what I'm
dedicating the next phase of my career
to bringing the science that we know
that we talked about to the table for
vision engineering and in particular the
fact that there are there really are 20
or so distinct cell types and they send
different types of visual information to
the different targets in the brain I
like to think of them a little bit as uh
an orchestra playing a symphony each
different cell type has its particular
score the violins do one thing the obos
do something else it's a very organized
signal coming out of the retina
presenting to the brain this complex
pattern of electrical activity that the
brain assembles into our visual
experience well current retinal implants
unfortunately are too crude to do
anything like that the the conductor has
just scattered the sheet music
everywhere and people are playing
whatever it's cacophony okay you can
maybe recognize a tune in there a little
bit sometimes navigate toward a doorway
but you're not going to get the full
richness of the experience by ignoring
the different cell types and I'm so
passionate about this in part for
reasons that a little bit are similar to
your reasons for doing this kind of work
that you do which I think is
great which is I I feel we have a
mission to give back as scientists to
take all this stuff we've been talking
about because we find it so interesting
and
cool and to deliver something to the
society that has allowed us to explore
these fascinating areas and in our case
it's in my the case of my lab and what
we've done it's to turn around and say
wait a second we understand that there's
these different cell types we understand
a lot about what they do none of this
information appears in current epir
retinal implants can't we do better by
using the science to restore Vision in a
way that respects the circuitry of the
retina that's what we're trying to do
and the mismatch is intense um I I told
you when we were adding
before that nothing that we have learned
about the retina since the founding of
the national Eye Institute in
1968 is incorporated into the existing
retinal implants nothing we've learned a
ton about the retina your research was
funded by the national Eye Institute my
research is funded by national ey
Institute a fantastic organization that
allows us to learn all these things how
is this showing up in the
neuroengineering to restore Vision to
people well currently it's not
and so we're trying to do that now doing
that turns out to be hard and maybe
we'll talk about that it's a it's a
technological feat that's really
challenging you have to build a device
that you can implant in a human that can
recognize the distinct cell types see
where they are stimulate them separately
from one another and conduct this
Orchestra to create a musical score that
reasonably closely resembles the natural
one that's what we're all about doing
and as it turns out and maybe we'll talk
about that separately that mission of
being able to restore the patterns of
activity that the retina normally
creates also has extremely exciting
spin-offs in three directions one of
them is understanding better how the
brain puts the signals together that's
research for the brain the second one is
augmenting Vision creating novel types
of visual Sensations that weren't
possible before and maybe doing
something along the Elon Musk lines of
delivering more visual information than
was ever
possible and third figuring out how to
interface to the brain more broadly
because as you and I know the structure
of the retina is very much
representative of the structure of many
brain areas and if we're going to figure
out how to interface to the visual
cortex we darn well bitter figure out
how to interface to the retina first
that's what we're all about doing in my
lab these days is figuring out how to do
that well that's a mixed science and
engineering effort we've done about 15
years of basic science on that how do we
stimulate cells how do we recognize
cells how are we going to build a device
that does all this and talks to the
cells in this way and I can go into lots
of gory detail about it um but that's
what we've been doing the basic research
on and the last few years we've worked
at Stanford with um fantastic Engineers
from various disciplines electrical
engineers material scientists others to
figure out how to put together the
pieces and build an implant that can do
this in a living human so is the idea to
build a robotic retina to build a a
essentially an artificial retina that
could be put into the eye of a blind
person or even put into the eye of a
sighted person that would fundamentally
change their ability to see or in the
latter case uh enhance their ability to
extract things from the visual world
that they would otherwise not be able to
see like like seeing twice as far um
getting you know hawk-like resolution of
the visual World um yep or which that
would be cool yep could be distracting
yep like I'm not sure I want to see the
the fine movements of a piece of paper
in somebody's notebook from across a
cafe as they flutter the pages um but
you might want to for a moment there
might be a moment when you want to and
if you have an electronic device that
you can control that you can dial in to
sense different aspects of the visual
World Under You Know by by your choice
you might be like yeah that's pretty
cool I want to be able to do that right
now there's an example I like to give
which I think maybe is is helpful for
interpreting what we're talking about
when we say being able to do more things
with the optic nerve you gave the
example of many voices and stuff here's
an example that I like we know that we
can drive down the road and have a phone
call
handsfree and do that quite safely
pretty safely right and you're why
because you're tapping in you've got two
types of signals coming into your brain
your visual signal of the cars on the
freeway any one of which could kill you
in an instant so it's
important and the sound coming into your
ears which carries the voice of your
girlfriend that's telling who's telling
you something that you're interested in
hearing and these are different parts of
the brain processing this information
and so you can do both of these things
at the same time because there's no
interference one part of the brain is
working doing one thing another part's
doing something else you're good what
you can't do is to read your texts and
drive down the freeway at the same time
that's not good because now that visual
system of yours that needs to be
detecting these fast moving dangerous
objects is being distracted by looking
at the text and you might die and some
other people might die with you so I see
a lot of people texting and
driving yeah that's why I like to point
out this example to remind people you
can't do it well it's like it's like you
can't do it well you probably talk yeah
it used to be you know we'll just take a
brief uh tangent here into this topic um
a few years back there were there were a
lot of news articles a lot of discussion
about texting and driving a lot of
attention to getting people to stop
texting and
driving I've seen a few people pulled
over for texting and driving before but
I would say texting and driving is
rampant reading what's on one's phone y
while driving is rampant yep all you
have to do is be on the freeway here in
Los Angeles look in the car next to you
yep look where they're looking and
people like reading and texting while
driving presumably when they're doing
that they're just using their peripheral
vision to detect any kind of motion and
um no doubt this has caused the deaths
of many people yeah change lanes get
away from them and you know just just
like that other driver so so here's the
thing um and this is this is uh I say
this a bit tongue and cheek but it's
it's sort of a real example it may be
that if we harness the different cell
types in the
retina to deliver different visual
information to different cell
types like the image of the text on your
screen to a certain cell type that you
know the so-called
cells or the motion of the objects in
the visual scene the cars to a different
cell type cells by the way folks
because they're very very small yes and
by named by anatomist decades ago so we
carry that nomenclature forward sure um
and the parasol cells which are
different cells that you can potentially
encode the movement of the cars in the
parasol cells and if those two systems
are operating independently which we
sort of think they may be from research
that you know very well from your
extensive studies and vision
um maybe we can do those two things
safely at the same time now by the way
that's not my research goal to text and
drive at the same time just to be clear
but it's a very tangible real world
example of if we do really have parallel
Pathways that can be modulated and
controlled independently of one another
this opens the door to streaming all
kinds of visual information in parallel
into our very high band with visual
systems that wasn't possible during
Evolution because we didn't have control
over the cell types so I think of that
as the world of visual augmentation and
it starts to get interesting if the
different cell types are behaving in an
independent way and when they transmit
visual information to the brain now how
are we going to figure that out well we
need a device that can stimulate the
different cells independently and then
study that to see whether people can and
can do this kind of thing right what's
that device the artificial retina the
same implant I'm telling you about that
can restore Vision to people because
it's an electronic device that can up in
the activity in the different cell types
that same device is what we can use as a
research instrument to understand if the
different pathways are parallel if the
signals interact with one another and
explore how the brain receives that
information and then we can use that to
explore can we augment vision and allow
allow ourselves to have new visual
Sensations that we don't even know what
that would look like we we we don't even
understand what it would look like to us
to see those Sensations but it might be
able to deliver lots of information to
our brain and if we can do all those
those things then we can take that same
set of tools and Engineering
Technologies into the brain to access
different cell types as well I'd like to
just take a quick break and acknowledge
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docomo here of of what you've done um
you started off with the understanding
that the neural retina is perhaps the
best place to try and understand how the
brain works because of its Arrangement
the cell types Etc you spend a number of
decades doing these wild experiments um
on human retinas and other retinas um
recording the different cell types with
these high density What I Call Bed of
nails two and a half decades I'm not
that two and a half decades um it's your
uh robustness that matters EJ um and you
have plenty of it um you figure out what
the cell types are so then you gained an
understanding of how light is
transformed into different types of
electrical signals that encode different
features in the visual scene then comes
the challenge of developing
neuroengineering tools to try and
stimulate the specific cell types in a
way that more or less mimics their
normal patterns of activation like not
um activating a huge piece of retina so
that you know the cells that like
increases in redness are also being
stimulated with the cells that like you
know edges in a way that would create
some shoy like crazy representation of
the outside world no you want the same
Precision that light stimulation of
these cells in the intact human eye
provides in this explanted retina this
retina on this bed of nails but then a
device that essentially can mimic what
the retina does and you needed to do all
that earlier work understanding like
what does the normal retina do what does
the healthy retina do in order to try
and develop this prosthetic device to
either restore Vision
or because it puts puts you in the
position of being able to stimulate
cells however you want in theory you
could create a situation in a human
where the cells that respond to um I
don't know outlines of objects are are
hyperactive so that you
know the person could um effectively see
objects in one's environment better than
anyone else yeah could perceive I know
motion is a tricky one but motion better
than anyone else could see detail in the
visual world that no one else could
detect we're not talking about turning
people into mantis shrimp um but the
analogy works because mantis shrimp can
see things that we can't and vice versa
and so what you're talking about here is
neural augmentation through the use of
engineering yep and we often do talk
about it as sci-fi because the Sci-Fi
writers have been talking have been you
know writing about this for decades it's
not sci-fi anymore it's sigh it's
straight up sigh right now it's really
we just need to build the
instrumentation and start working with
those experiments to figure out how to
make make it work I think we have a
responsibility to do this because this
is the way we take this kind of
information all that's been learned
about the visual system by the national
Eye Institute since since 1968 and all
the people that it's funded to do this
research and turn the corner and make a
difference for Humanity with it and I I
assume and think that Humanity will be
leveraging nervous system knowledge to
build all sorts of devices that we can
interface to the world with I think you
know I don't know Elon Musk but I think
he's right about that that that's where
we're
headed it should be done well it's
important to do it well um we will
hopefully be more connected to truth in
the world if we're able to build devices
that give us better Sensations more
acute understanding of what's going on
out there better abilities to make
decisions and all that let alone just
see stuff so that Frontier of developing
Technologies to allow our brains and our
visual systems initially and then other
parts of our brains to do things better
is unbelievably exciting it is SciFi but
I just want to emphasize I think it's
the responsible way to go to think about
how to do that well all technologies
that we develop can be used for good or
for ill and I'm sure some of your
listeners who are a lot a lot of very
passionate thinking people out there
thinking about neuroscience and the
implications worry what does this mean
we're going to be introducing electronic
circuits in our brains to do stuff yeah
well we will it's pretty much clear that
Humanity will do that and
so in any technology development you
have to think about well how do you do
it well how do you do it for good there
there are popular movies right now about
technology development such as
understanding the structure of the
atom and that technology development can
be used for good or for ill to blow up
cities or to save
civilizations how's it going to go well
I think I think as scientists we're
responsible for advancing that in a
thoughtful and meaningful way I think we
can do this in the retina it is the
place to start it's the and you know you
I'm curious what you think actually as a
scientist your background is in this
field or very close field to mine I know
you speak with all sorts of scientists
on this podcast um but this is pretty
much your field or very close not the
neuroengineering part but understanding
the retina I'm curious if you agree that
this is the place to start doing this
stuff the first guest ever asked me a
question on this podcast during a guest
interview um I think this would be a fun
place to both answer and Riff on this a
little bit because um first of all I
think the retina is absolutely the place
to start because we understand so much
of what it does what the cell types are
but maybe by comparison a different
brain region the hippocampus which is
involved in the formation of memories
and other stuff but formation of
memories about what one did the previous
day what one did many years ago Etc is
an area that I think anytime the
conversation about neural Prosthetics or
neuroengineering or neuro augmentation
comes up people think oh wouldn't to be
cool to have like a little stimulating
device in the hippocampus and then if I
want to remember a bunch of information
from a page or from a a lecture I just
stimulate and then voila all the
information is batched in there um while
that's an attractive idea I think it's
worth pointing out right now that sure
there is a pretty decent understanding
of the different cell types in terms of
their shapes some of their electrical
properties of the hippocampus but there
is in no way shape or form the depth of
understanding about the hippocampus and
what the individual cell types do and
what the different layers of it do that
one has for the neural retina so what
we're really saying is if you stimulate
the hippocampus you'll likely get an
effect but it's unclear what the effect
is and it's not clear how to stimulate
that's to me the best reason to focus on
the retina because you know what the
cell types are thanks to the work of
your laboratory and many other
Laboratories you know what sorts of
stimulation matter and it provides the
perfect test bed for this whole business
of neuro augmentation neuro neuroeng
engineering I think there's also a
bigger discussion to just frame this in
which is so much of what we discuss on
this podcast with guests and in Solo
episodes relates to things like dopamine
neur neuromodulator serotonin and
everyone is interested in these things
because they can profoundly change the
way that we perceive and interact with
the world but one only has to look to
the various Pharmaceuticals that
increase or decrease these
neuromodulators and know that indeed
those Pharmaceuticals can be immensely
beneficial to certain individuals I want
to be clear about that but that whatever
quote unquote side effects one sees or
lack of effect over time is because
those receptors are like everywhere over
the around the brain so you can't just
increase dopamine in the brain and
expect to only get one specific desired
effect yes so the reason you're here
today um is not because we both worked
on the retina and it's not because we
happen to also be friends it's because
uh to my mind your laboratory represents
the um Apex of precision in terms of
trying to figure out what a given piece
of the brain in your case the neuro
retina does parse all its different
components and then use that knowledge
to create a real world technology that
can actually tickle and probe and um
stimulate that piece of the brain in a
way that's meaningful right not just
like sending electrical activity in and
that to me is so important I think if we
were going to think about levels of
specificity for manipulating the human
brain to get it an effect you would say
okay crudest would be drugs take a drug
increases serotonin which might bind to
particular receptors let's take the drug
psilocybin a lot of excitement about
psilocybin we know that can lead to
increased connectivity between different
brain Reg at rest there's probably there
is some demonstrated clinical benefit
there's also some potential hazards but
it's very broad scale we don't know
what's happening when the person is
thinking about a uh you know a piece of
moss expanding into an image and a
memory of their childhood or it's like a
million different things are happening
there and then at the other far extreme
is the kind of experiment that you're
talking about stimulating one known type
of retinal
cell seeing what that means for visual
processing or modeling what that means
means for visual processing and then
building a device that can do exactly
that and then maybe ramp it up 20% 50%
and because I think that represents the
first step into okay how would you
stimulate the hippocampus to create a
super memory would you stimulate a
particular cell type in a particular way
and to my knowledge There's You know
despite the immense excitement
about the hippocampus and understandably
so there just isn't that precision and
of understanding yet so uh forgive the
long answer but you know you ask me a
question on on this podcast give a long
answer yeah and it specificity is what
you're talking about and we need
technology to do that to to modulate
neural circuits in a highly specific way
we got to start with the piece of the
neural circuit we understand best and we
have best access to that's the retina
it's sitting right there on the surface
we can get right into it and in install
devices we know so much about it that's
the place to start the place that we
understand build Electronics that is
that is adaptive that senses what
circuit it's embedded in and responds
appropriately it's not just Electronics
you stick in there and it does something
and that's it no it it first figures out
who it's talking to and then learns to
speak the language of the nearb neural
circuitry so a smart device smart device
let's push on that a little bit so
um put a little chip onto the retina
that can stimulate specific cell types
is there a way that it can use AI
machine learning that it can learn
something about the tissue it happens to
be in contact absolutely in the simplest
possible way the device Works in three
simple Steps step number one record
electrical activity which is what we do
in our lab in a room full of equipment
but this is a 2mm size chip implanted in
your eye record the electrical activity
just recognize what cells are there when
they're firing what electrical
properties they have to identify the
cells and cell types in this specific
circuit in this human that's step one
step two stimulate and record so you
figure out oh this electrode activates
cell number 14 with 50% probability this
electrode activates cell number 12 if
you pass a micro amp of current with
this probability and so on you make a
big table that tells you how these
electrodes talk to these cells in your
circuit that's step two calibrate the
stimulation by stimulation and recording
then finally when you have a visual
image and you want to represent it in
the pattern of activity of these cells
you say okay I know from Decades of
basic science what these cells ought to
be doing with this image that's coming
in I know exactly what they ought to be
doing that's what the science has been
telling us we've been studying the
neural code for decades to understand
this I know what they should do use my
device with my calibration where I know
where the cells are I know how the
electrodes talk to them and bing bing
bing bing bing activate them in the
correct sequence that's what I think of
as a smart device a device that records
stimulates and records and then finally
stimulates yes AI is part of that of
course it is because this is a very
complex uh transformation if you will
from the external visual world to the
patterns of activity of these cells it's
not easy to write down in just a few
lines of code or in a few equations it's
complicated and AI is really helpful for
that and learning by stimulating and
recording and aggregating information
quickly so that you can then use the
device that's absolutely a part of the
engineering it let me be clear the AI
doesn't help us to understand it's just
an engineering tool that helps us to
capture what this thing normally does
and then go ahead and execute and make
it do the thing it should normally
do I hope people um will appreciate this
example uh perhaps not you know not but
goodness I don't know 40 50 years ago
but still today uh one treatment for
depression is electric shock therapy uh
a very you know on the face of it
barbaric um treatment but effective in
certain conditions it's still used for a
reason um but it can appear barbaric
right you know people are have like a
bite you know a bite device you know so
they don't um bite through their tongue
or their lips they're you know they're
strapped down and they stimulate the
whole just like stimulate all neurons in
the brain essentially there's a huge
dump of neurotransmitters and
neuromodulators it's like drugs it's
completely non-specific stimulation
effectively probably even less specific
than drugs maybe and yet the clinical
outcomes from electric shock therapy in
some cases are pretty impressive like
people um the brain is quote unquote
reset they still remember who they are
um but presumably through the the the
release of neuromodulators like dopamine
serotonin acetylcholine in a very
non-specific way there has been some
symptom relief in some cases what you're
talking about is really the opposite
extreme um you know before I said
Pharmaceuticals that tickle a particular
neurom modulator pathway would be the
opposite extreme I think electric shock
therapy is probably the the the most um
extreme where is this whole business of
neural prosthesis going outside of the
visual system like right now um I can
imagine that there are little
stimulators in the spinal cord for sake
of restoring movement to paralyze people
um I realize this is not your field but
is are you seeing impressive stuff there
um or is it still really really early
days there's absolutely impressive stuff
uh particularly uh for example people
reading out signal
from the motor cortex or the language
cortex in order to help people to
communicate or to move cursors on
screens in order to interact with
devices these are paralyzed people par
yeah excuse me paralyzed people who
can't interact with technology the way
that we do um and but with their
thoughts can send signals through an
electronic device that can be used to
control a mouse on a screen and have
them connect to the internet that's a
huge deal to be able to have people do
that imagine how life changing would be
to be able to communicate if you
couldn't before so there are wonderful
examples of that you know of them so do
I the work of Krishna shanoy and Jamie
Henderson at Stanford is one beautiful
example over the recent years Eddie
Chang doing stuff now uh you know
neuralink doing doing this kind of stuff
the built on the work of Shino and
Henderson and stuff so that's great um
you know stimulating in spinal circuits
as you said for creating rhythmic
movements that's that's happening
so this is an enormous space and in each
case what you said I think is really
highly relevant that electroshock
therapy you can think of that as look
let's say your computer is not behaving
right you can reboot it might work then
it'll start not working again then you
have to reboot it again well how often
do you want to reboot your computer it
gets a little inconvenient to be
rebooting your computer every five
minutes maybe you want to go in and
actually diagnose this thing and put in
a piece of software that fixes the thing
that was going wrong instead of
rebooting your computer every 5 minutes
right and I think of electric shock
therapy a little bit as a reboot um it's
that level so we want to intervene more
specifically how do you do that well you
have to understand the software in order
to do that you have to have specificity
controlling this thing in your computer
not this this this this or this this
particular thing that's going wrong you
got to interfere with that and change it
and modulate it well that's what
understanding the neural circuit is
about that's what building specific
Hardware that can activate specific
cells is
about that's in in the case of the
retina again it's just so obvious that
it's right in front of us to do this
stuff and it's right in front of us to
take us into augmentation to giving us
better senses a fun example I like this
is it's an interesting topic because the
National Institutes of Health that um
funds a lot of research that goes in
this direction tends to not be
interested in augmenting our senses they
kind of want to they they draw a line
more or less at saying look we're trying
to restore what we were as humans not
create a new kind of
human and that's an interesting question
because I don't think there is a fine
there's an actual line a bright line
between those things I don't think
there's a bright line between those two
things the the finest example I know is
that even in the very crudest visual
restoration devices you have to actively
suppress the infrared sensitivity of
your camera
to not have infrared vision why because
many cameras are sensitive to infrared
light so in other words if you don't put
an infrared filter in front of your
camera you're going to have some
infrared vision maybe it won't help you
very much whatever I'm just trying to
say as soon as you start building
devices to restore Sensations building
electronic devices augmentation is right
around the corner it'll creep up on you
real fast so I I think you you can't
even really draw a
line throughout today's discussion we've
been thinking of the brain as kind of a
the rest of the brain I should say
because the neural retina is two pieces
of the brain extruded out into the eye
Globes during development I like to
remind people of that over and over when
you're looking at somebody's eyes you
are looking at two pieces of their brain
um so no debate about that but most
people don't realize that you'll never
look at anyone the same way again but
this is the reason why you can tell so
much about people's inner state from
their from their eyes somebody who's
sleep deprived it's not just about the
droopiness of their eyelids or the
circles under their eyes there's a
there's an aliveness to the eyes the the
yogis um talk about um people that sort
of show up at the level of their eyes as
opposed to sunk back into their brain
you know these are very um kind of
abstract Concepts but they and there's
some very non-abstract stuff these days
looking at looking through the eye at
the retina the way the op
opthalmologists do and there's a lot of
diagnostic capability just in those
images of the rtina oh right there I'm
glad you brought this up there's um some
uh interesting and increasing evidence
that looking at the neural retina
because it is a piece of the brain with
neurons that have the potential to both
Thrive or degenerate that looking at the
neural retina which one can do with
these new technologies um can provide a
window into um whether or not there are
forms of degeneration such as
Alzheimer's and other forms of neurod
degeneration deeper within the brain
that one can't image directly because of
the the thick opacity of the skull right
so in other words Imaging the eye in
order to determine if someone is
developing in Alzheimer's because you
have a direct view into a little piece
of the brain it's a it's a good signal
it can help you figure stuff out about
what's going on in your brain even
beyond the sunken eyes
absolutely amazing so I think the rest
of the brain piece is is also really
interesting and maybe here we can go
like semi neuro philosophical um you
know that there are clearly parts of the
brain that are involved in um essential
what I call housekeeping functions
regulating respiration you know keeping
us breathing keeping our heartbeating um
digestion um responding to threats in in
some sort of basic way like through the
secretion of adrenaline and and giving
us the potential to move but a lot of
the brain is is um capable of plasticity
and um one wonders if you were to for
instance develop a retinal
prosthesis that would allow me to um see
with twice the level of detail that I
currently can would my adult brain be
capable of dealing with that information
we're talking about twice as much
information coming in same brain tissue
on the receiving end can it make sense
of it do we have any idea if it can make
sense of it are there um are there
experiments that speak to that yeah
that's a fantastic and interesting
question it makes you think about neural
development all over again right and I I
take some inspiration on that from the
work of someone you know Eric nson um
who discovered that there is plasticity
beyond the period periods of time he
discovered many wonderful things but
there's plasticity well beyond the
period of time that we thought that
there was plasticity in certain animals
and in particular that if you make
gradual adjustments to the sensory world
you can exhibit plasticity that you
can't see if you make an Abrupt
adjustment so plasticity is there it
just has to be brought on by more subtle
manipulations that take you from A to B
in little incremental steps and if you
take those incremental steps you can see
the adult
plasticity so coming to your
question is the brain capable of
receiving the kind of extra information
we provided could be that if we just
show up on day one bam try to deliver
twice the visual resolution or whatever
in your visual your visual
system it could be that if we try to
deliver twice the visual resolution on
day one it won't work you'll see It'll
you know it won't look sensible to you
but if we gradually introduce it by the
way that we're dialing up the resolution
we may be able to get there and there
are fascinating studies to be done you
think about Spike timing dependent
plasticity a term that that your viewers
may not all know but is a is related to
how neurons adjust their strength of
connectivity to one another according to
the timing of the signals in those cells
mechanisms like that tell us wow the
brain really cares about the very
precise timing of stuff and to the
degree that that influences the way that
neurons do or don't strengthen their
connections to one another it's so
fundamental in everything from memory to
visual function what have you this
relates to fire together wire together
although um it highlights the Together
part how closely in time do two neurons
need to be active in order for them to
subsequently increase their connectivity
and indeed one of them needs to be
active a little bit before the other one
in order for it to work optimally right
so if it what I what I Envision is that
when we have full control of the neural
code with an electronic implant that can
talk to the cells and do all the things
that I said and we can really control
the neural code coming out of the retina
we can then start to play games and dial
up that neural code very slowly and
teach the remaining brain how to
understand these signals not introduce
some crazy thing from day one no just
gradually teach isn't that how we do
everything well isn't that how
plasticity
works I love the uh subtlety and the uh
rationality of your example because you
know so much of what we see in the
internet and on the news is like you
know chips inserted into the brain to
create super memory or uh you know
conversations between you know 50 people
at the same time without anyone speaking
you know just hearing other people's
Thoughts by way of um you know neural
signals being passed from one to the
next but yet another reason why you're
here today is because you represent the
the the realistic grounded um
incremental approach to really parsing
this whole thing of how the brain works
and how one then goes about um
engineering devices to augment the human
brain and as you just pointed out it's
not going to be done by just sticking
electrodes in and stimulating and seeing
what happens in fact those experiments
were done in the 1960s people like
Robert Heath would put electrodes into
the brain during neur surgery stimulate
and just see what the patient would do
or what they reported thinking you know
nowadays that's done still but with a
lot more precision and intention and
we've moved we've moved far beyond that
by the way I just want to say those were
important first experiments the first
thing got to do Keith was was was a
rather um let's be honest not not the
most Savory character he he embarked on
some experiments that um had a social
agenda to them and was a pretty pretty
uh at least by my read was was not the
kind of person I'd want to spend time
with to say the least but but you're
right those experiments were critical
because like electric shock therapy like
the formulation of drugs that can
massively increase certain neurom
modulators or decrease them they LED to
some level crude but some level of
understanding about how the brain works
which is what we're really talking about
today yep um but you represent the uh as
I said the the astronauts of this
astronauts don't go into space and just
kind of blast off and see where they end
up there's a there's there's math
there's physics uh there's computer
science sensors cameras right looking
where are we about to land here on the
moon is there a crater here or not what
what's around us we we should sense
what's there and then make our decisions
accordingly and our electronic implants
in the brain really we should make them
smart why make them dumb we're smarter
than that we can build implants that can
sense what's around them and change
their patterns of activity
accordingly I I use a metaphor sometimes
if you go to if you go as an American
who doesn't speak Chinese to China and
you start yelling in English maybe
somebody will to to learn which way to
go on the street somebody might
understand you at some point and help
you out but it's going to be a it's
going to be a you know not very
effective way to get around it's way
better if you speak the language you
talk to people and ask ask them where to
go so that's what we need to know we
need to say look we have the science we
have incredible devices we can engineer
we have ai now that even helps us to do
this query of the outside world and turn
it into a smarter instrument make our
instruments smart make them so they know
how to talk to the brain don't expect
that the brain is just going to wrap
itself around your your simple
electronic device no make a smart device
that's what we want to make a smart
rental
implant maybe we could just take a
couple of minutes and talk a little bit
about you and the some of the things
that have led to your choice to go in
this direction
so did you always know you want to be a
neuroscientist from the time you started
college what was your trajectory I
should know this but I you were an
undergraduate at at Princeton at
Princeton that right studying math math
so you could have just done all your
work with a piece of paper and a pen but
you had to try and engineer all these
electrodes okay that's a pen and paper
pen I took a very random route I studied
math as an undergrad I spent a few years
running around playing music and
traveling living a Bohemian life well
tell me more about that oh it was I
basically just told you all I'm going to
tell following the Grateful Dead no not
quite following them but uh it was that
was an important part of the story um
and important part of your personal
development um yes very much so uh free
Expression Dance music creative
exploratory music all that kind of stuff
such a contrast to the the EJ that comes
forward when we're talking about the
Precision of neural stimulation in in
the in specific retinal cell types but I
think it's useful for people to hear
both young and old like um that uh one's
nervous system can be partitioned into
these different abilities like go and
dance and travel and you you weren't
doing anything academic at that at that
time no for a few years I wasn't doing
that programming computers to make a to
make a living and uh then I started I
started three different PHD programs at
Stanford before I simultaneously no no
no in sequence I started in the math PhD
program I learned that was not really
for me and I started in a in an
economics PhD program in the business
school there and I realized after after
less than a year that was not for me um
I worked in a startup company for a
while I did a lot of stuff for a few
years and it took some settling um but
then I decided to go into nurse science
and there were a couple formative things
one is that I had I had gotten a really
formative experience as an undergraduate
from a wonderful guy called Don ready
who taught a introductory Neuroscience
course who was really inspiring Mentor
um and then when I when I was at
Stanford I met Brian wandell my PhD
adviser and I was inspired by him I
thought I didn't know why he was
studying what he was studying but I just
knew I wanted to learn from this man and
I wanted to study with him I just knew
this was this was the person who should
be my mentor based on something about
him yes C can I ask you about these
three PHD programs because I think
people here um you know or or see what
you're doing and and probably imagine a
very linear trajectory but now I'm
hearing you you like tour it around
playing music then you start a PhD
program nope then another one nope then
another one without getting into all the
details I mean were there nights spent
lying awake thinking like what am I
going to do with my life or did you have
the sense that you knew you wanted to do
something important you just hadn't
found the right fit for you like how how
much anxiety on a scale of 1 to 10 10
being total panic um did you experience
at at the Apex of your anxiety in that
kind of wandering am I allowed to go
above 10 like turning up the amp to 11
sure I just think it's really important
for people to hear whether or not they
want to be scientists or not this idea
that people that are doing important
things in the world uh in my view um um
rarely if ever understood that that's
the thing that they were going to be
doing there was some wandering about
that sure seems like it doesn't it yeah
I I I experien the same when I talk to
other people and it seems like that and
for sure for me uh it just took a while
of trying different things to see number
one what I was really good at and where
I felt I could make a difference and it
and I realized um I studied math and I
was okay at math but I know I I have
known mathematicians who are really
talented gifted mathematicians the one
who really make a difference I wasn't
going to be one of those people likewise
playing music I don't have that
intrinsic Talent it's fun I can play
songs in front of people and do stuff I
like it and stuff like that but I don't
have that kind of talent in fact I'll
say something that that I say to friends
sometimes and you're a good friend of
mine if I had the talent to get a few th
people on their feet dancing by playing
music I'd probably just do that really
as long as we've been friends I knew
none of this I like knew none of this
mostly because I think we always end up
talking about Neuroscience or other
aspects of our life um but I I didn't
know I I know I know a great many things
about you but I had no idea it's so
interesting um do you still do dance we
had Eric Jarvis on the podcast by the
way Professor Rockefeller who studies um
at one point was studying um uh Speech
in so in Birds um and song in Birds and
then he's done a great many other things
now in genetics of of vocalization and
you know he actually uh danced with or
was um about to dance with the Alvin ay
Dance Company it's like a really really
talented dancer um uh and so you know
dance seems to be like a theme that
comes up among the Neuroscience guests
on this podcast do you still dance yeah
I love to dance I'm a free form dancer I
don't I'm not a skilled dancer but I
love I love music I love dancing I think
it's part of the human spirit I someday
will understand the Neuroscience behind
dancing Dan in right dancing is a
universal human thing in all cultures
what is this dancing thing why do we do
this and other creatures don't well
Jarvis thinks that um perhaps it's one
of the more uh early forms of language
and that song came before spoken
language it's sort of interesting that
birds that um can actually recreate
human speech oftentimes have the ability
to dance as well oh wow um and and so
there's some commonality of circuitry
there we'll provide a link to that
episode jar really I would love to hear
that I mean I but if I may I just I'd
like to Riff on that in a different in a
different way um I did spend some time
wandering around as many people do um
and I think particularly for your young
listeners and viewers who don't know wow
you know could I ever be a scientist and
develop new things stuff like that yes
you can and if you're messing around
your life trying this trying that trying
the other thing definitely stick with it
keep looking for the thing that works
for you I I really deep believe that you
got to play around you got to find what
it is that works for you interestingly
enough at least it's interesting for me
I I spent a lot of years studying the
retina in a pure basic science just
curiosity driven research way as you and
I have both done in the
past
um and as it turned
out I learned all the stuff I needed to
know about the retina to do to develop a
high fidelity adaptive retinal implant
of the type that I'm talking about in
that process the technology the
stimulation recording figure out the
cell types how do you stimulate all
stuff I learned all that stuff and I
have come to a point in my life where I
realize wow if somebody's going to do
what I think needs to be done which is
to take everything we've learned about
the retina and instantiate that in in
smart technology that can restore vision
and do all the things we've been talking
about who who are the people in the
world who have the right training and
background and knowhow to do that stuff
I I'm one of them I I know that and it's
totally by chance that I picked up and
learned or it seems by chance that I
picked up and learned the things that I
need to know for this so but but I'm I
definitely have the right knoow to do
this based on all my training and the
research that I've done and it feels
accidental sometimes I look back on my
own history I'm like how did I get here
where this is obviously the thing I need
to do was this this on purpose it didn't
seem like it was on purpose but now I
got to do this because I know what needs
to be done and it's something that needs
to be done so that's that's my mission
for the you know coming decade or so
wild I I mean I knew you had this
engineer matthy uh geeky Neuroscience I
don't want to say geeky cuz I'm well
because it makes it sound like I'm not
right there in the same same uh raft
with you but but I didn't know about
this more free-spirited um move in all
directions depending on what one feels
the moment dancing uh EJ it's very cool
um are you still a a absolute level 11
coffee snob yes okay yeah I used to go
to meetings and um EJ would bring his
own coffee maker and coffee to to
meetings we're not talking about an
espresso machine we're talking about
like extreme levels of coffee snobbery
press pot the correct ground coffee
correct kind of press byot good good
good I I expect nothing less uh proof
that um not all circuits in the brain
are neurop plastic nor should they be
that's right but to bridge off of that
in a more serious way um despite the the
free you know free exploration aspect to
yourself and and that hopefully other
people don't suppress um it seems like
you you really are um good at develop
like knowing your taste like it seems
like the the I think it was the great
Marcus Meister a colleague of ours who
you know has also worked on the neural
retina extensively of course once said
you know that there's a coding system in
the brain that leads to either the
perception the the feeling of um yum
yuck or me and that so much of life is
being able to register that in terms of
who you interact with and how and um the
the choices of problems to work on it
seems like you have a very keen sense of
of like yes that and you move toward
that you've always been very goal
directed um since the time I've known
you so and and you've picked such a a a
huge problem but going about it in in
such a precise way hence the the analogy
to the space space mission so um like
when you experience that um may ask is
it does it come about as like a thought
like oh yeah that has to be the thing or
is it like a whole body sensation what a
great question I love that question I
have two things to say to that the first
is that for me it's all it's all
feeling I I don't make hardly any
decisions out of thoughts I think I
process I put it all into the hopper and
the hopper comes out and spits out a
feeling and feeling's like yeah that's
the thing to do 100% And I know not
everybody's like me lots of people
aren't like me and particularly lots of
scientists aren't like me that you know
so but but I definitely roll that way
that is absolutely how I work there's
there's something that's related to that
that I think is you know philosophically
in terms of personal development and
Spiritual Development stuff I think is
quite relevant that I think you'll
you'll relate to my favorite aphorism is
know
thyself the
Oracle and I I think because if you
don't know yourself you can't do
anything you don't even know where to go
you can't even you know Orient yourself
at the next thing in your life and I
think it deserves to have um two Aries
that go with it or
aenda uh know thyself be thyself which
is not easy it's not easy to really be
yourself in this world there are all
sorts of things telling us to be
something other than what we
are and the third one is love
thyself and it's you know having gone
through
much exploration of yourself and your
life and your values and my and me too
and all the things we've talked about
over time that's not easy some of us are
not necessarily programmed to love
ourselves and uh it's a
skill I and I really I try my best to be
with those three things all the time
know thyself be thyself love thyself
could you elaborate a little bit more on
your process for the third I this is a
concept that um has been very
challenging for for me and I think for
many other people um and it gets um
kind of opaque when it starts getting
complete with like self-respect and and
Etc like like loving thyself do you have
practices um do you meditate um do you
Journal do you spend time um trying to
cultivate a love for self yeah yeah I'm
I meditate in an informal way in the
morning with my coffee every morning I
make a fantastic cup of coffee and I sit
with it I believe you for five or 10
minutes and take in my world as it's
coming toward me and start to be as I as
I come into the day and come into
Consciousness I I I meditate like that
and I have a aanga related yoga practice
many of you many of your viewers and
listeners will know about Ashtanga Yoga
it's a very physical spiritual
traditional yoga practice that has a
deep meditative and breath Focus
component I know you've had lots of
episodes and discussion about the breath
and the importance of that for awareness
um you know at the end of a of many
Western Yoga practices you end with
Namaste which is expressing your respect
and for the connectedness of what is in
front of you to the whole universe and
what's common to all of us and
everything and I usually practice yoga
by myself and when I say namaste at the
end of my yoga practice a part of that
is to myself earlier when I asked you
about how you guide your decisions you
said it's all feel and you provided a
beautiful description as to how and why
that occurs for you and your trust in
that I don't recall you saying whether
or not the feeling is in your head or
it's a whole body feeling does it have a
particular signature to it that you'd be
willing to share is it excitement that
makes you want to get up and move or is
it a a Stillness I think I I ask because
we've been talking throughout today's
episode about you know the Precision of
neural coding and these signals that are
at the level of individual cells and And
yet when it comes to feeling we actually
have a a pretty crude map and certainly
a deficit in language to explain what
this feeling thing is and I I know that
people experience life and feelings
differently but I think it's often
insightful when somebody uh with your
understanding of the nervous system and
yourself can share a bit like what does
it feel
like I love that question and it relates
to something you said to me years
ago uh what it feels
like uh is
ease and I remember years ago when we
were talking about challenging things
that each of us was facing in our lives
you said to me something like I I wish
for you some ease with all of this it
was very um moving touching as that's
what a good friend does is to give that
to somebody to who they love and um um
and it sticks with me probably 10 years
later so
um the feeling I feel when I'm on the
path that makes sense for me is ease
it's there's just nothing it's just okay
this is
it I love that I don't actually recall
that specific conversation because we
had many many conversations sitting in
your yard in San Diego on those plastic
chairs with your
um with my Bulldog Costello hanging out
by the way folks EJ knew Costello my
Bulldog Master very well and he was not
a huge fan of dogs prior to meeting
Costello but um Costello flipped him he
he became a at least a Costello lover I
love Costello I'll never forget him yeah
he embodied
ease he did nothing but sleep and eat uh
he he embodied um energetic efficiency
and everybody loves him everybody who
gets to be in the same room with him
loves him the people I just spoke to in
your setup here your colleagues you know
yeah I could see why and you have a
beautiful photo of him hanging there
yeah yeah he's a what a creature a great
great memory definitely embedded in my
nervousness I often choke up when I
think about but I I want to be clear
because I've already cried once about
him on a different podcast I don't want
to do that today they're not tears of
sadness it's this crazy thing like I
love him so much I just kind of want to
explode so damn it costell got me again
and publicly again so he's someplace
laughing so I I love that um and I think
if um if I made you know do you think
it's worth kids and adults learning to
recognize those those kind of States
those signals that tell them they're on
the right path by paying attention
to I don't know this like like we said
there's sort of a deficit of language
like EAS is in the body eases in the
mind it's the release of I mean you know
it's not even worth exploring verbally
because it's a is such a whole body
whole nervous system thing yeah I I I
feel like I I actually was thinking
about I was giving advice to a young
fellow who uh is applying to graduate
school recently and had a zoom call with
him about stuff and he had received some
good advice from some other people and
then I gave him some advice and I saw
him and speak and emote and with body l
language drop into like oh yeah that
makes sense yeah that that feeling of
course kind of the of course and I think
if you can teach people to do that I
don't know if the verbal communication
of that is going to like you said is
that going to do anything but can you at
least observe it in them as a teacher as
a mentor and do things and when you know
when you've done it because you see them
drop into ease do you think you can
detect ease in people by looking at them
and seeing their body body language and
everything it's it's got to be an
amalgum of different things that the
Cadence of their breathing their pupil
size it's not worth dissecting this is
an experiment I would not want to run
yes right I wouldn't want to bring
people into a laboratory and figure out
you know what pupil of the eye Dynamics
combined with certain rhythms of
breathing relaxation of the shoulders
because it's too beautiful for that is
it's too beautiful and it's it's too
nuanced and um it's different when we're
in Motion versus when we're lying down
it's like I mean science is capable of a
great many things but I don't think
needs to be pointed at every aspect of
Human Experience I think they um some of
these things are are simply worth
allowing to just be do you feel the same
way about when you when you have a
feeling about a person you meet somebody
and their energy just captures you it's
like wow what a cool person what what
amazing energy do you want to know the
science behind that I don't no I don't I
think the the word that comes to mind
when I experience somebody like that or
something like a animal or you see
something the movement of something or a
beautiful piece of music or something is
uh the word just
behold yeah I just want to stop and and
take in as much of it as possible and
here's something I know you've done but
I'm checking to make sure I really got
this right because I've done it too
because we sometimes get human retinas
for doing our experiments the first
thing that happens when we get the human
retina we bring it back to our lab it's
a big production everybody's getting
ready to go a whole bunch of moving
Parts going on we have to open up the
eye and look into it to see what
condition it's in and it's typically on
with a dissecting scope on a chair and
it's open sitting on a chair dissecting
scope looking down look into the
eye it is so beautiful it it's
breathtaking each time I've looked at
the retina I don't know how many times
each time wow this is what's
initiating all the visual experiences
I've ever had in my life or that person
ever had in their life right and the
beauty just keeps coming I love it and I
love it because you're talking
about a behold moment that isn't just to
entertain your curiosity sure it's that
you want to understand how the brain
works um but also a behold moment that
leads from that desire to understand to
a deep level of understanding now after
you know more than two decades of
exploration to a mission in service to
humanity restore Vision to the blind
develop neuroprosthesis and other types
of neuroengineering technologies that
will allow the human brain to function
better than it would otherwise so
there's real purpose there too so it uh
represents kind of a perfect ecosystem
of it's not just about delighting in
something and and um and spending one's
time there there's a real there's a real
Mission there so um I love
it well EJ Dr
cheski uh Dr huberman I rarely get
called that these days um when I invited
you here today I was absolutely sure
that uh our listeners and viewers were
going to get a absolutely worldclass
explanation of how the nervous system
works and the the retina and the visual
system in particular and um that it
would be delivered with the utmost
Clarity which it was so thank you I know
there's been so much learning in and
around that and you beautifully framed
for us what that means in terms of the
larger understanding of how the nervous
system works and what you and other
Laboratories are now in a position to
really do with that information and the
technologies that are being built and
that will be built and you know the
purpose in bringing you here today was
was just that but not that alone um you
know I think we hear so much about the
brain and how it works and everyone
wants to have tools and protocols to
function better but um
it's clear that the work that you're
doing is headed in a Direction that's
going to vastly expand the possibilities
for sake of treating human disease and
and for expanding Human Experience I'm
I'm certain of
that what I did not expect
however was that when I wrote down one
bullet point well actually two I wrote
still a coffee snob question mark the
answer is yes um and yoga you know that
we would end up in territory where you
would share some of your experience that
I myself was not aware of about this um
a bit of a Wandering um of three
different PHD programs and of this um
cultivation of an intuitive sense of of
beauty and taste and preference
that the way you described it takes you
out of your rational mind and into the
aspects of your nervous system that just
really act as a compass toward what is
absolutely right for you and we're all
so lucky that what's absolutely right
for you turns out to also be what's
absolutely right and beneficial for the
world so thank you for coming here today
thank you for sharing your
knowledge and your heart and for doing
it with um such an incredible degree of
of openness and respect so thank you so
much thank you Andrew it's a great
pleasure really appreciate it thank you
for joining me for today's discussion
with Dr EJ chisi to learn more about the
work in the chich niski lab and to find
links to EJ's social media handles
please see the links in the show note
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