November 19, 2024 • 26 mins
In this special episode of Neuroscience Perspectives, host John Foxe, PhD, director of the Del Monte Institute for Neuroscience at the University of Rochester, sits down with S. Murray Sherman, PhD, Maurice Goldblatt Professor of Neurobiology at the University of Chicago, in Chicago at the annual Society for Neuroscience (SfN) conference. Sherman is a neuroscientist known for his groundbreaking work on the thalamus. Dive into a compelling conversation that unravels how the thalamus plays a pivotal role as the brain's relay center, transforming sensory input into meaningful perceptions and actions.
Discover how Dr. Sherman's research sheds light on the thalamus's intricate connections to cortical regions, revealing its role in shaping critical cognitive functions. From vision to decision-making, his work was integral in informing the understanding of the visual pathway from the retina through the thalamus to the cortex, and it also revealed other cortical areas organized in parallel to direct connections.
Learn how mentors and a bit of luck played critical roles in his journey, including Nobel laureates Richard Feynman, PhD, Roger Sperry, PhD, and Ray Guillery, PhD, who would become Sherman's longtime collaborator.
Link to Sherman's SfN profile piece.
Whether you're a neuroscientist or just interested in the brain —listen, learn, and subscribe to Neuroscience Perspectives today!
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Episode Transcript
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(00:00):
And I realized, and the message I give to students today is,
(00:04):
it's important that you be smart enough and work hard enough and all these other things.
Those are necessary but insufficient to be successful.
There's a lot of luck involved and you don't have control over that.
That's true.
And I have been extremely lucky and I'm not going to go into other stories about that,
but it's very humbling to appreciate that.
(00:32):
I'm John Foxe, Director of the Del Monte Institute for Neuroscience at the University of Rochester,
and I'm delighted to welcome you to another episode of Neuroscience Perspectives.
We've taken the podcast on the road this year and we're here in lovely Chicago at the Society
for Neuroscience meeting, and I'm absolutely honored to be joined by Professor Murray Sherman,
the Maurice Goldblatt Professor of Neurobiology at the University of Chicago.
(00:55):
His research uses the visual and somatosensory pathways to study thalamic functional organization
and thalamic cortical relationships.
His work has been integral to informing our understanding of the visual pathways.
He's a recipient of the Sloan and Guggenheim Fellowship
and has an honorary degree from Oxford University.
Murray, thanks so much for being here with us today.
(01:17):
Thank you for inviting me.
Most, probably most people out there didn't really know much about the thalamus at all,
but if you think of somebody going through a basic, you know, Neuroscience 101 course,
they'll learn that this is this little structure in the middle of the brain and it acts as a relay,
but it's so much more than that.
Are there a few things you want to say about like the importance of the thalamus?
(01:37):
I'm going to start off with an anecdote.
In the 1980s, I happened to be in London.
I've told this story to many, many people, but probably not to your audience.
I was in London and the Museum of Natural History there
announced a new display they had on the human brain.
I was a tourist there.
(01:58):
I thought it would be fun to go in and see what this looked like.
When I walked into the exhibit, the first thing I saw was a large three-dimensional
model of the human visual system in which they had the retina projecting directly to cortex.
They left it out.
No thalamus.
I was naturally a bit upset.
I mentioned that just because it indicates how far the appreciated thalamus has come.
(02:22):
Nobody would do that today, I'd like to think.
So yes, but textbooks still depict the thalamus as
merely to get information from the periphery to cortex.
For instance, in the visual system, they'll mention maybe that the retina projects to the
lateral geniculate nucleus, which is part of the thalamus that projects to cortex,
(02:43):
and that's all it gets.
Most of thalamus by still textbook views is ignored and is pretty much an enigma.
What Ray, Guillory, and I emphasize was actually most of thalamus we now recognize
is there to serve as a communication hub between cortical areas.
(03:04):
That means that most of thalamus is playing a very important role in how cortex functions
writ large.
And it's not just there to relay information from the periphery, but it is very important
in cortical functioning and how cortical areas communicate together and coordinate for
important cognitive functions.
Excellent.
So I think that's where we are today.
(03:25):
And I think finally, this has caught hold in the field.
Right, right.
I mean, correct me now if I'm wrong, like in the visual nucleus, this lateral geniculate
nucleus, actually the major inputs, the bulk of the inputs are coming back from cortex
rather than coming from the periphery.
They come back from cortex, but this may be a bit too technical.
(03:46):
There are two kinds of excitatory pathways in the brain.
And this is something else that Ray and I worked on.
One is we call driver.
It carries information.
The retina input to the lateral geniculate nucleus is a driving input because it's
carrying the information.
The feedback from cortex to the LGN, to the lateral geniculate nucleus, is what we call
(04:08):
modulatory.
It's not carrying basic information, but it is affecting through complicated modulatory
synaptic functions the gain of retinogeniculate transmission and other factors of retinal
input and how it's relayed to cortex.
So that distinction, we think, is very important to parse out how circuits operate to
(04:30):
understand how you identify drivers versus modulators in thalamic and cortical
circuitry.
And then there's been a couple of decades of extraordinary work on oscillatory dynamics
and cortex and that, but the first place I read about changes in modes of information
(04:51):
transfer was in burst and tonic modes by Sherman and Guillory.
Yeah, so thalamic relay cells can operate in two different kinds of firing mode, which
are called, as you said, burst and tonic.
And we think that the tonic mode, I don't want to go into too much technical detail.
(05:14):
Sure.
Because it is a bit complicated.
I'll just say that the tonic mode is what we would call a very linear mode.
There's not a lot of distortion in the signal.
And the signal that it transfers to cortex, which is a very reliable copy of the retinal
input, has a relatively weak influence on cortex.
(05:35):
But it gets there.
The burst mode is a much more active mode, a very high frequency barrage of action
potentials.
It's very nonlinear.
It does not portray a very reliable map of what's going on in the periphery.
There's a lot of nonlinear distortion, but it provides a very powerful input to cortex.
(06:01):
We call it a wake-up call.
It's when no retinal signal has been coming by for a long time, there are mechanisms that
cause the relay cell to switch to burst mode.
So when a new signal comes along, it alerts cortex.
Something's coming along now, you better pay attention to it.
Very good.
That's sort of a poor man's description of what we think is going on.
(06:22):
But it's a very elegant one.
That feedback from cortex that I mentioned is important for controlling which of those
two modes is going to be happening in the relay.
Right.
So much more complicated dynamics than that little tiny nucleus in the thalamus.
It's complicated.
But I guess the take-home message is that the information being relayed by the thalamus
(06:46):
can either be a pure information route or a wake-up call after a lot much has been happening
that now things are going to start happening and we pay attention to it.
One of our major connections, which is the great Ray Guillery, who was your longtime
collaborator.
Yes.
And just open the floor to tell us a little bit about you and Ray and how you got together
(07:08):
and how meaningful that was.
Ray was absolutely vital to my career right from the beginning.
I met him when I was a graduate student.
I think it was 1968 and he really impressed me from the beginning because he invited me
to Wisconsin where he was at the time to talk about my thesis research and he treated me
(07:30):
like his equal, not as a student, right from the beginning.
For whatever reason he took a liking to me and we were collaborating ever since.
It's a collaboration that lasted almost 50 years until he died in 2017.
But we started off by working on some research projects together in the 70s and that eventually
(07:54):
evolved to more theoretical workings that we were doing.
We wrote three monographs, a number of theoretical essays, and it was a delight for me to work
with him and everybody that knew him and I'm sure this is true of you as well, loved the
man and respected him.
He was such an important person in the field.
(08:15):
Deeply decent human being and a titan in the field and you two boys really wrote the book
on thalamus.
Well, he was a titan in the field and the reason I'm here is largely because of his
influence.
Yeah.
I can't say enough about that.
Outstanding.
Usually the question is about, I have the great honor of being the editor-in-chief of
(08:38):
the European Journal of Neuroscience and Ray was the first editor of the journal when it
started in 1989.
So did you have much interaction with him?
Oh, just a little bit.
Of course, the connection was through Paul Bolam who was very close with Ray and was
the co-editor with me at the time.
But of course, it's shoulders of giants.
I mean, it's a great legacy for me personally to have been connected to that.
(09:01):
The one thing about Ray is that he was in one way an old-fashioned traditional anatomist,
but he always thought functionally, which was unusual for neuroanatomists at that time.
And that's what made him special, I think.
Yeah.
And so that's a great point.
I jump an off point really.
This sort of transition from the era of anatomy and really trying to trace out the circuits
(09:24):
and understand those circuits to thinking about them functionally.
And you really had a first row seat to that transition.
Would you tell us a little bit about that and how you think about, let's say, your grounding
in anatomy going onwards from there?
Yeah.
I like to point out that when I started as a graduate student, there were, I think, no
neuroscience departments.
(09:46):
Neuroscience was not recognized as a field.
People interested in the brain tended to work in anatomy departments or physiology departments
or psychology departments.
And the field obviously has, during my career, has emerged to become one of the most important
fields in biomedical research, which I think is a good example of why correlation doesn't
(10:09):
mean cause and effect.
Right.
But I was privileged to see all that happen during my career.
And I always felt that neuroscience is one of these fundamental issues that humans have
been concerned about since long before history was recorded.
(10:30):
That and cosmology are the two main things.
So it's every university, every major research entity should have something like neuroscience
as part of what it's doing.
And that more and more universities now have it as a central part of their research program,
(10:52):
which I find a real sign of the importance of the field today.
Yeah.
And if I may say it, I mean, the emergence of neuroscience as an important field is because
of folks like you and Ray and the people that did.
I say that seriously.
I know you're modest about these things.
(11:12):
Tell me how you found neuroscience.
What was the trajectory?
What does young Murray Sherman, youngster?
Okay.
So the Society for Neuroscience has a series of short autobiographies written by some senior
people.
And I wrote one of these.
(11:32):
So anybody who's interested in the details can find it there.
It's available online.
I don't want to be too repetitive, but I'll tell you my story.
There's a lot of name dropping.
I have to say in advance.
I wanted to be a physicist from early days in high school, as long as I can remember.
And I wanted to go to the college that had the best physics.
(11:57):
And for me at the time, that was Caltech.
That's where I went.
Right.
And we happened to be the only class that Richard Feynman taught.
So he taught us for two years.
Richard Feynman, for those that don't know, was a fairly famous Nobel laureate in physics.
He was a very entertaining teacher.
And he would often stop teaching physics and tell anecdotes.
(12:23):
And every so often he would stop and say, he knew that most of you guys, because there
was only men there at Caltech, there were no women yet, I want to be a physicist.
But I'm telling you a much more interesting area to do research in is brain research.
Neuroscience wasn't a word then.
And he said that several times.
(12:43):
I'd like to think that that had a big impact on me.
It may have, but honestly I'm not certain.
But maybe coincidentally, after my first year, I wanted a summer job there.
And one opened up, now another name is dropping, in Roger Sperry's lab.
He was another Nobel laureate.
So I just basically started summer work in his lab.
(13:03):
And he was a famous neuroscientist.
And I caught the bug then.
And from then on, that's all I wanted to do.
Wow.
And you wanted to be a physicist.
Can we go back a little?
I mean, wow.
To run into Feynman at Caltech and then to end up with Roger Sperry, that's quite...
Yes, I know.
Two good rolls of the dice right there.
(13:24):
Well, the one thing that I emphasize in what I wrote is how much serendipity plays a role
in this.
And I had to do a lot of introspection when I was asked to write this piece.
For the first time, it was a great experience for me.
And I realized, and the message I give to students today is, it's important that you
be smart enough and work hard enough and all these other things.
(13:46):
Those are necessary but insufficient to be successful.
There's a lot of luck involved and you don't have control over that.
That's true.
And I have been extremely lucky.
And I'm not going to go into other stories about that.
But it's very humbling to appreciate that.
And yet, right, I think that's a crucial point.
There's a lot of luck and happenstance of being around when a technology takes off or
(14:07):
a specific theory comes around.
But you have to also have your eyes open and you have to be open to luck.
And that's another message, right?
You have to take advantage of luck when it avails itself.
Yes, that's true.
Tell me, can we backtrack even from Caltech?
When did you know you had the science bug?
(14:28):
Is this a childhood thing?
Did it come on later?
I was always very, I was a good student in school.
I enjoyed math and science quite a bit.
And I remember Sputnik came up as a shock to the country.
And it seemed patriotic to want to be a scientist and not allow Russia, the USSR at the time,
(14:51):
to get ahead of us.
And so my interest and actually love of math and physics that I had in high school, I had
a physics teacher in high school that was fantastic, sort of made its mark on me.
And that's what I wanted to do.
That's wonderful, wonderful.
(15:11):
Little patriotism thrown into the mix as well.
That's fantastic.
When you look at the current, fast forward, 2024, when you look at neuroscience today,
where are the opportunities?
And are there local minima?
Are there cul-de-sacs we're running down that you think we're wasting our time on?
(15:34):
So a bit of the positive and the negative here.
Yeah, I'm not sure about that.
Trying to predict the future is hopeless as far as I'm concerned.
It's so unpredictable.
The only thing I would say that I think is missing in a lot of people's thinking about
the brain is the grounding in evolution.
And there are several missteps that I think are made because of that.
(15:58):
There's too much, I think, too much emphasis on cerebral cortex.
When my view is cortex is obviously important, but cortex didn't evolve to do anything that
hasn't already been involved by subcortical circuits to do with maybe the exception of
language and a few other things.
So I wish there was more of an evolutionary approach to studying the brain.
(16:21):
I'm not sure how big a deal that is, but that's the one thing that I preach a lot.
Other than that, I think predicting where the field is going and the only other thing
I would say that is a detriment is when I think when we were both younger, there were
(16:41):
a lot of models to study the brain, lots of species being studied.
And right now it's almost all mice and monkeys.
And we work mostly on mice.
And I think the challenge is always to come up with a question that you think is going
to be generalized to mammals and not limited to mice.
(17:02):
I'm not interested in mouse brains per se.
I'm interested in what that can tell us about animals.
That becomes increasingly difficult because we don't have the stepping stones of other
species to figure out what's actually general to mammals.
I'm not sure why that came about.
Probably funding agencies weren't so positive as they used to be about having a broad selection
(17:25):
of species to study.
But I think that is a problem going forward.
So it's a mistake to walk away from that sort of evolutionary chain, the fact that we have
different complex.
The thinking of evolutionary approaches to neuroscience used to be strong and is not
here today.
Yeah.
Yeah.
And do you worry?
I mean, there's also a withdrawal from non-human primate work as well around the sort of political
(17:47):
landscape.
Does that worry you?
Yes, it does, because I think working in non-human primates is essential, absolutely essential.
And I know if there's a lot of pressure, for instance, we just were told that there's a
bill in Congress to prevent the VA from supporting any more non-human primate research and feline
(18:08):
research as it happens.
Things like that would be devastating to the field, not just for the animals, but for humans.
I don't think people really understand the importance of animals to human health and
wellness.
But I'm also...
It's a battle we're losing really in the media and in publicity, right?
(18:31):
We're not doing a good enough job, I think.
And I'm a little disappointed at the number of universities that are backing away from
this and not standing up for what they should know better.
Agreed.
Yeah.
It's a tough time for universities.
They're under a lot of pressure.
Yeah, tough.
I wouldn't want to be a university president now, that's true.
(18:52):
But I see that as a threat to the field going forward.
Yeah.
Absolutely.
Absolutely.
And do you see a way forward there?
In some ways, we're being outflanked by the anti-scientific world in social media and
media in general.
And of course, we don't have training in media, right?
It's not like we get fundamental training in how to communicate like that.
(19:13):
Yeah, I agree.
And people are losing their faith in science.
This is all about my pay grade.
I recognize the problem.
I'm not sure we can do about it because people like me aren't trained or have particular
talents in getting to the general public.
In fact, as you know, I've written quite a bit, a lot with Ray.
(19:35):
We've written books.
We made an attempt at one point to write for the general public.
And I hadn't appreciated until we made that attempt and failed, by the way, how difficult
that is.
It is difficult.
People that can have a new respect for people that do that and do that well.
Right, right.
I think that's extremely important.
And that needs to be improved a lot because if the general public understood better what
(19:59):
was going on, I think we get the support that we need.
Right.
But we're not doing a good job of educating the general public.
There was even a period where we would shower scorn on the people who walked into that science
space because they were painting with broad strokes and generalizing, but they were doing
(20:20):
a great service to the community.
We were picking nets.
That was silly.
Yes, I agree.
Hopefully, we've changed our view about that and recognized that's an important niche that
needs to be filled.
I think that's a really important point to make.
You also served in a lot of leadership roles.
One of our points of contact is as fellow chairs of neuroscience departments and medical
(20:41):
schools and that.
Tell us a little bit about your leadership style and challenges that came up over the
years or just your thoughts about leading in the current academic environment.
I don't think there are any real tricks to it.
My own approach is to delegate a lot because let other people bring other people into positions
(21:05):
where they have some authority.
And of course, you always want to be honest and truthful people.
And you have to learn to say no.
That's hard for some people.
Right.
I'm not sure there's any particular trick.
Some people either come by naturally or you're not going to be good at it.
Not everybody is good at doing that sort of thing.
(21:27):
I enjoyed the leadership role and I always recognized for myself in academics that as
far as I wanted to go as chair of a department because I felt as chair, I was still a real
faculty member.
I don't mean this in a negative sense, but I would never want to be a dean or a provost
or anything like that.
(21:49):
I greatly admire those people who do it well.
That's important.
I just know that I would fail at it.
That's all.
So leadership in general, I'm not sure what that means.
There are certain kinds of leadership that I feel comfortable doing and others that I
wouldn't.
Gotcha.
Yeah.
If I may say, I think one of the things and having also had a seat watching University
(22:11):
of Chicago's neuroscience department thrive over the years, that having somebody in the
leadership role with vision who has the reputation that you have, that's a big part of it too.
It provides an on-ramp for people and it provides a vision and it provides a way forward.
Yes.
That was a new department that I took over.
We started it.
(22:31):
I'm extremely proud about the way it panned out.
I'm very proud of that.
I get much too much credit for it.
I could live with that.
But it worked because of the fact that the administration, the deans and the provost
were very supportive the whole way through.
It couldn't have been done without them.
There were a number of key faculty, neuroscience faculty in leadership when I arrived that
(22:54):
also were extremely important and helpful.
They don't get much credit for this.
So it was a team effort.
Again, I'm proud of it and it is what it is now.
As I mentioned before, I'm no longer the chair and I'm now glad for that because I realized
there were a lot of things I was doing as chair, administrative things and bureaucratic
(23:18):
things that I'd just as soon not be doing anymore.
David Friedman is my colleague in the department.
He's the new chair.
He's fantastic.
The department's in good hands so I feel good about all of it.
Excellent.
Well, I really appreciate you being here.
I have one more question because I think a big component of our audience are young trainees
(23:38):
coming into the field and people think about graduate school.
And I always ask this question, looking at the field right now in 19, 19, in 2024, what
would you say to a youngster coming into the field?
What do they need to keep their eyes open for and is it a good time?
(23:59):
Would you advise for one of your own nieces or nephews?
That's a great question.
Great question.
I would, but there'd be some hesitation to it because my concern is that people coming
through now have a tougher time of making it than when I was a student.
(24:22):
It was pretty easy for me.
There aren't as many openings.
If you really want to succeed in this field, it's imperative that you be able to compete
successfully for funding, mostly from NIH or NSF or equivalent.
That's become much more difficult as well.
And all I can say is that if you take the risk and are able to do those things, there's
(24:45):
no better career.
I mean, it's been fantastic.
I feel like I've been doing a hobby I love and I'm getting paid for it.
But I would, if I'm really being honest and giving advice, I want them to make sure they
understand the risks.
And the upside of that is that we're seeing students come into our programs now to get
(25:10):
PhDs.
10 or 15 years ago when I asked them, because I always ask students what they want to do
in their careers, the answer was they want to be an academic scientist.
Now less than half say that because they recognize the problems.
They want to go into industry.
So getting a PhD and sometimes even going further with postdoctoral training is still
(25:33):
valuable if you want that career.
So what I would advise students is if you're at all interested, you don't have to decide
now you can get this kind of training.
And maybe at the end of that time, things will be different than they are today.
You don't have to decide now.
I guess that's the advice I would give.
(25:53):
Excellent.
Murray, I can't say how great an honor it is to get to know you personally over the
last few years and just to have you here on the Earth Science Project.
Feeling is mutual and I really appreciate you asking me to do this.
Thank you so much.
Thank you.
And I realized, and the message I give to students today is,
(00:04):
it's important that you be smart enough and work hard enough and all these other things.
Those are necessary but insufficient to be successful.
There's a lot of luck involved and you don't have control over that.
That's true.
And I have been extremely lucky and I'm not going to go into other stories about that,
but it's very humbling to appreciate that.
(00:32):
I'm John Foxe, Director of the Del Monte Institute for Neuroscience at the University of Rochester,
and I'm delighted to welcome you to another episode of Neuroscience Perspectives.
We've taken the podcast on the road this year and we're here in lovely Chicago at the Society
for Neuroscience meeting, and I'm absolutely honored to be joined by Professor Murray Sherman,
the Maurice Goldblatt Professor of Neurobiology at the University of Chicago.
(00:55):
His research uses the visual and somatosensory pathways to study thalamic functional organization
and thalamic cortical relationships.
His work has been integral to informing our understanding of the visual pathways.
He's a recipient of the Sloan and Guggenheim Fellowship
and has an honorary degree from Oxford University.
Murray, thanks so much for being here with us today.
(01:17):
Thank you for inviting me.
Most, probably most people out there didn't really know much about the thalamus at all,
but if you think of somebody going through a basic, you know, Neuroscience 101 course,
they'll learn that this is this little structure in the middle of the brain and it acts as a relay,
but it's so much more than that.
Are there a few things you want to say about like the importance of the thalamus?
(01:37):
I'm going to start off with an anecdote.
In the 1980s, I happened to be in London.
I've told this story to many, many people, but probably not to your audience.
I was in London and the Museum of Natural History there
announced a new display they had on the human brain.
I was a tourist there.
(01:58):
I thought it would be fun to go in and see what this looked like.
When I walked into the exhibit, the first thing I saw was a large three-dimensional
model of the human visual system in which they had the retina projecting directly to cortex.
They left it out.
No thalamus.
I was naturally a bit upset.
I mentioned that just because it indicates how far the appreciated thalamus has come.
(02:22):
Nobody would do that today, I'd like to think.
So yes, but textbooks still depict the thalamus as
merely to get information from the periphery to cortex.
For instance, in the visual system, they'll mention maybe that the retina projects to the
lateral geniculate nucleus, which is part of the thalamus that projects to cortex,
(02:43):
and that's all it gets.
Most of thalamus by still textbook views is ignored and is pretty much an enigma.
What Ray, Guillory, and I emphasize was actually most of thalamus we now recognize
is there to serve as a communication hub between cortical areas.
(03:04):
That means that most of thalamus is playing a very important role in how cortex functions
writ large.
And it's not just there to relay information from the periphery, but it is very important
in cortical functioning and how cortical areas communicate together and coordinate for
important cognitive functions.
Excellent.
So I think that's where we are today.
(03:25):
And I think finally, this has caught hold in the field.
Right, right.
I mean, correct me now if I'm wrong, like in the visual nucleus, this lateral geniculate
nucleus, actually the major inputs, the bulk of the inputs are coming back from cortex
rather than coming from the periphery.
They come back from cortex, but this may be a bit too technical.
(03:46):
There are two kinds of excitatory pathways in the brain.
And this is something else that Ray and I worked on.
One is we call driver.
It carries information.
The retina input to the lateral geniculate nucleus is a driving input because it's
carrying the information.
The feedback from cortex to the LGN, to the lateral geniculate nucleus, is what we call
(04:08):
modulatory.
It's not carrying basic information, but it is affecting through complicated modulatory
synaptic functions the gain of retinogeniculate transmission and other factors of retinal
input and how it's relayed to cortex.
So that distinction, we think, is very important to parse out how circuits operate to
(04:30):
understand how you identify drivers versus modulators in thalamic and cortical
circuitry.
And then there's been a couple of decades of extraordinary work on oscillatory dynamics
and cortex and that, but the first place I read about changes in modes of information
(04:51):
transfer was in burst and tonic modes by Sherman and Guillory.
Yeah, so thalamic relay cells can operate in two different kinds of firing mode, which
are called, as you said, burst and tonic.
And we think that the tonic mode, I don't want to go into too much technical detail.
(05:14):
Sure.
Because it is a bit complicated.
I'll just say that the tonic mode is what we would call a very linear mode.
There's not a lot of distortion in the signal.
And the signal that it transfers to cortex, which is a very reliable copy of the retinal
input, has a relatively weak influence on cortex.
(05:35):
But it gets there.
The burst mode is a much more active mode, a very high frequency barrage of action
potentials.
It's very nonlinear.
It does not portray a very reliable map of what's going on in the periphery.
There's a lot of nonlinear distortion, but it provides a very powerful input to cortex.
(06:01):
We call it a wake-up call.
It's when no retinal signal has been coming by for a long time, there are mechanisms that
cause the relay cell to switch to burst mode.
So when a new signal comes along, it alerts cortex.
Something's coming along now, you better pay attention to it.
Very good.
That's sort of a poor man's description of what we think is going on.
(06:22):
But it's a very elegant one.
That feedback from cortex that I mentioned is important for controlling which of those
two modes is going to be happening in the relay.
Right.
So much more complicated dynamics than that little tiny nucleus in the thalamus.
It's complicated.
But I guess the take-home message is that the information being relayed by the thalamus
(06:46):
can either be a pure information route or a wake-up call after a lot much has been happening
that now things are going to start happening and we pay attention to it.
One of our major connections, which is the great Ray Guillery, who was your longtime
collaborator.
Yes.
And just open the floor to tell us a little bit about you and Ray and how you got together
(07:08):
and how meaningful that was.
Ray was absolutely vital to my career right from the beginning.
I met him when I was a graduate student.
I think it was 1968 and he really impressed me from the beginning because he invited me
to Wisconsin where he was at the time to talk about my thesis research and he treated me
(07:30):
like his equal, not as a student, right from the beginning.
For whatever reason he took a liking to me and we were collaborating ever since.
It's a collaboration that lasted almost 50 years until he died in 2017.
But we started off by working on some research projects together in the 70s and that eventually
(07:54):
evolved to more theoretical workings that we were doing.
We wrote three monographs, a number of theoretical essays, and it was a delight for me to work
with him and everybody that knew him and I'm sure this is true of you as well, loved the
man and respected him.
He was such an important person in the field.
(08:15):
Deeply decent human being and a titan in the field and you two boys really wrote the book
on thalamus.
Well, he was a titan in the field and the reason I'm here is largely because of his
influence.
Yeah.
I can't say enough about that.
Outstanding.
Usually the question is about, I have the great honor of being the editor-in-chief of
(08:38):
the European Journal of Neuroscience and Ray was the first editor of the journal when it
started in 1989.
So did you have much interaction with him?
Oh, just a little bit.
Of course, the connection was through Paul Bolam who was very close with Ray and was
the co-editor with me at the time.
But of course, it's shoulders of giants.
I mean, it's a great legacy for me personally to have been connected to that.
(09:01):
The one thing about Ray is that he was in one way an old-fashioned traditional anatomist,
but he always thought functionally, which was unusual for neuroanatomists at that time.
And that's what made him special, I think.
Yeah.
And so that's a great point.
I jump an off point really.
This sort of transition from the era of anatomy and really trying to trace out the circuits
(09:24):
and understand those circuits to thinking about them functionally.
And you really had a first row seat to that transition.
Would you tell us a little bit about that and how you think about, let's say, your grounding
in anatomy going onwards from there?
Yeah.
I like to point out that when I started as a graduate student, there were, I think, no
neuroscience departments.
(09:46):
Neuroscience was not recognized as a field.
People interested in the brain tended to work in anatomy departments or physiology departments
or psychology departments.
And the field obviously has, during my career, has emerged to become one of the most important
fields in biomedical research, which I think is a good example of why correlation doesn't
(10:09):
mean cause and effect.
Right.
But I was privileged to see all that happen during my career.
And I always felt that neuroscience is one of these fundamental issues that humans have
been concerned about since long before history was recorded.
(10:30):
That and cosmology are the two main things.
So it's every university, every major research entity should have something like neuroscience
as part of what it's doing.
And that more and more universities now have it as a central part of their research program,
(10:52):
which I find a real sign of the importance of the field today.
Yeah.
And if I may say it, I mean, the emergence of neuroscience as an important field is because
of folks like you and Ray and the people that did.
I say that seriously.
I know you're modest about these things.
(11:12):
Tell me how you found neuroscience.
What was the trajectory?
What does young Murray Sherman, youngster?
Okay.
So the Society for Neuroscience has a series of short autobiographies written by some senior
people.
And I wrote one of these.
(11:32):
So anybody who's interested in the details can find it there.
It's available online.
I don't want to be too repetitive, but I'll tell you my story.
There's a lot of name dropping.
I have to say in advance.
I wanted to be a physicist from early days in high school, as long as I can remember.
And I wanted to go to the college that had the best physics.
(11:57):
And for me at the time, that was Caltech.
That's where I went.
Right.
And we happened to be the only class that Richard Feynman taught.
So he taught us for two years.
Richard Feynman, for those that don't know, was a fairly famous Nobel laureate in physics.
He was a very entertaining teacher.
And he would often stop teaching physics and tell anecdotes.
(12:23):
And every so often he would stop and say, he knew that most of you guys, because there
was only men there at Caltech, there were no women yet, I want to be a physicist.
But I'm telling you a much more interesting area to do research in is brain research.
Neuroscience wasn't a word then.
And he said that several times.
(12:43):
I'd like to think that that had a big impact on me.
It may have, but honestly I'm not certain.
But maybe coincidentally, after my first year, I wanted a summer job there.
And one opened up, now another name is dropping, in Roger Sperry's lab.
He was another Nobel laureate.
So I just basically started summer work in his lab.
(13:03):
And he was a famous neuroscientist.
And I caught the bug then.
And from then on, that's all I wanted to do.
Wow.
And you wanted to be a physicist.
Can we go back a little?
I mean, wow.
To run into Feynman at Caltech and then to end up with Roger Sperry, that's quite...
Yes, I know.
Two good rolls of the dice right there.
(13:24):
Well, the one thing that I emphasize in what I wrote is how much serendipity plays a role
in this.
And I had to do a lot of introspection when I was asked to write this piece.
For the first time, it was a great experience for me.
And I realized, and the message I give to students today is, it's important that you
be smart enough and work hard enough and all these other things.
(13:46):
Those are necessary but insufficient to be successful.
There's a lot of luck involved and you don't have control over that.
That's true.
And I have been extremely lucky.
And I'm not going to go into other stories about that.
But it's very humbling to appreciate that.
And yet, right, I think that's a crucial point.
There's a lot of luck and happenstance of being around when a technology takes off or
(14:07):
a specific theory comes around.
But you have to also have your eyes open and you have to be open to luck.
And that's another message, right?
You have to take advantage of luck when it avails itself.
Yes, that's true.
Tell me, can we backtrack even from Caltech?
When did you know you had the science bug?
(14:28):
Is this a childhood thing?
Did it come on later?
I was always very, I was a good student in school.
I enjoyed math and science quite a bit.
And I remember Sputnik came up as a shock to the country.
And it seemed patriotic to want to be a scientist and not allow Russia, the USSR at the time,
(14:51):
to get ahead of us.
And so my interest and actually love of math and physics that I had in high school, I had
a physics teacher in high school that was fantastic, sort of made its mark on me.
And that's what I wanted to do.
That's wonderful, wonderful.
(15:11):
Little patriotism thrown into the mix as well.
That's fantastic.
When you look at the current, fast forward, 2024, when you look at neuroscience today,
where are the opportunities?
And are there local minima?
Are there cul-de-sacs we're running down that you think we're wasting our time on?
(15:34):
So a bit of the positive and the negative here.
Yeah, I'm not sure about that.
Trying to predict the future is hopeless as far as I'm concerned.
It's so unpredictable.
The only thing I would say that I think is missing in a lot of people's thinking about
the brain is the grounding in evolution.
And there are several missteps that I think are made because of that.
(15:58):
There's too much, I think, too much emphasis on cerebral cortex.
When my view is cortex is obviously important, but cortex didn't evolve to do anything that
hasn't already been involved by subcortical circuits to do with maybe the exception of
language and a few other things.
So I wish there was more of an evolutionary approach to studying the brain.
(16:21):
I'm not sure how big a deal that is, but that's the one thing that I preach a lot.
Other than that, I think predicting where the field is going and the only other thing
I would say that is a detriment is when I think when we were both younger, there were
(16:41):
a lot of models to study the brain, lots of species being studied.
And right now it's almost all mice and monkeys.
And we work mostly on mice.
And I think the challenge is always to come up with a question that you think is going
to be generalized to mammals and not limited to mice.
(17:02):
I'm not interested in mouse brains per se.
I'm interested in what that can tell us about animals.
That becomes increasingly difficult because we don't have the stepping stones of other
species to figure out what's actually general to mammals.
I'm not sure why that came about.
Probably funding agencies weren't so positive as they used to be about having a broad selection
(17:25):
of species to study.
But I think that is a problem going forward.
So it's a mistake to walk away from that sort of evolutionary chain, the fact that we have
different complex.
The thinking of evolutionary approaches to neuroscience used to be strong and is not
here today.
Yeah.
Yeah.
And do you worry?
I mean, there's also a withdrawal from non-human primate work as well around the sort of political
(17:47):
landscape.
Does that worry you?
Yes, it does, because I think working in non-human primates is essential, absolutely essential.
And I know if there's a lot of pressure, for instance, we just were told that there's a
bill in Congress to prevent the VA from supporting any more non-human primate research and feline
(18:08):
research as it happens.
Things like that would be devastating to the field, not just for the animals, but for humans.
I don't think people really understand the importance of animals to human health and
wellness.
But I'm also...
It's a battle we're losing really in the media and in publicity, right?
(18:31):
We're not doing a good enough job, I think.
And I'm a little disappointed at the number of universities that are backing away from
this and not standing up for what they should know better.
Agreed.
Yeah.
It's a tough time for universities.
They're under a lot of pressure.
Yeah, tough.
I wouldn't want to be a university president now, that's true.
(18:52):
But I see that as a threat to the field going forward.
Yeah.
Absolutely.
Absolutely.
And do you see a way forward there?
In some ways, we're being outflanked by the anti-scientific world in social media and
media in general.
And of course, we don't have training in media, right?
It's not like we get fundamental training in how to communicate like that.
(19:13):
Yeah, I agree.
And people are losing their faith in science.
This is all about my pay grade.
I recognize the problem.
I'm not sure we can do about it because people like me aren't trained or have particular
talents in getting to the general public.
In fact, as you know, I've written quite a bit, a lot with Ray.
(19:35):
We've written books.
We made an attempt at one point to write for the general public.
And I hadn't appreciated until we made that attempt and failed, by the way, how difficult
that is.
It is difficult.
People that can have a new respect for people that do that and do that well.
Right, right.
I think that's extremely important.
And that needs to be improved a lot because if the general public understood better what
(19:59):
was going on, I think we get the support that we need.
Right.
But we're not doing a good job of educating the general public.
There was even a period where we would shower scorn on the people who walked into that science
space because they were painting with broad strokes and generalizing, but they were doing
(20:20):
a great service to the community.
We were picking nets.
That was silly.
Yes, I agree.
Hopefully, we've changed our view about that and recognized that's an important niche that
needs to be filled.
I think that's a really important point to make.
You also served in a lot of leadership roles.
One of our points of contact is as fellow chairs of neuroscience departments and medical
(20:41):
schools and that.
Tell us a little bit about your leadership style and challenges that came up over the
years or just your thoughts about leading in the current academic environment.
I don't think there are any real tricks to it.
My own approach is to delegate a lot because let other people bring other people into positions
(21:05):
where they have some authority.
And of course, you always want to be honest and truthful people.
And you have to learn to say no.
That's hard for some people.
Right.
I'm not sure there's any particular trick.
Some people either come by naturally or you're not going to be good at it.
Not everybody is good at doing that sort of thing.
(21:27):
I enjoyed the leadership role and I always recognized for myself in academics that as
far as I wanted to go as chair of a department because I felt as chair, I was still a real
faculty member.
I don't mean this in a negative sense, but I would never want to be a dean or a provost
or anything like that.
(21:49):
I greatly admire those people who do it well.
That's important.
I just know that I would fail at it.
That's all.
So leadership in general, I'm not sure what that means.
There are certain kinds of leadership that I feel comfortable doing and others that I
wouldn't.
Gotcha.
Yeah.
If I may say, I think one of the things and having also had a seat watching University
(22:11):
of Chicago's neuroscience department thrive over the years, that having somebody in the
leadership role with vision who has the reputation that you have, that's a big part of it too.
It provides an on-ramp for people and it provides a vision and it provides a way forward.
Yes.
That was a new department that I took over.
We started it.
(22:31):
I'm extremely proud about the way it panned out.
I'm very proud of that.
I get much too much credit for it.
I could live with that.
But it worked because of the fact that the administration, the deans and the provost
were very supportive the whole way through.
It couldn't have been done without them.
There were a number of key faculty, neuroscience faculty in leadership when I arrived that
(22:54):
also were extremely important and helpful.
They don't get much credit for this.
So it was a team effort.
Again, I'm proud of it and it is what it is now.
As I mentioned before, I'm no longer the chair and I'm now glad for that because I realized
there were a lot of things I was doing as chair, administrative things and bureaucratic
(23:18):
things that I'd just as soon not be doing anymore.
David Friedman is my colleague in the department.
He's the new chair.
He's fantastic.
The department's in good hands so I feel good about all of it.
Excellent.
Well, I really appreciate you being here.
I have one more question because I think a big component of our audience are young trainees
(23:38):
coming into the field and people think about graduate school.
And I always ask this question, looking at the field right now in 19, 19, in 2024, what
would you say to a youngster coming into the field?
What do they need to keep their eyes open for and is it a good time?
(23:59):
Would you advise for one of your own nieces or nephews?
That's a great question.
Great question.
I would, but there'd be some hesitation to it because my concern is that people coming
through now have a tougher time of making it than when I was a student.
(24:22):
It was pretty easy for me.
There aren't as many openings.
If you really want to succeed in this field, it's imperative that you be able to compete
successfully for funding, mostly from NIH or NSF or equivalent.
That's become much more difficult as well.
And all I can say is that if you take the risk and are able to do those things, there's
(24:45):
no better career.
I mean, it's been fantastic.
I feel like I've been doing a hobby I love and I'm getting paid for it.
But I would, if I'm really being honest and giving advice, I want them to make sure they
understand the risks.
And the upside of that is that we're seeing students come into our programs now to get
(25:10):
PhDs.
10 or 15 years ago when I asked them, because I always ask students what they want to do
in their careers, the answer was they want to be an academic scientist.
Now less than half say that because they recognize the problems.
They want to go into industry.
So getting a PhD and sometimes even going further with postdoctoral training is still
(25:33):
valuable if you want that career.
So what I would advise students is if you're at all interested, you don't have to decide
now you can get this kind of training.
And maybe at the end of that time, things will be different than they are today.
You don't have to decide now.
I guess that's the advice I would give.
(25:53):
Excellent.
Murray, I can't say how great an honor it is to get to know you personally over the
last few years and just to have you here on the Earth Science Project.
Feeling is mutual and I really appreciate you asking me to do this.
Thank you so much.
Thank you.
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