June 27, 2023 • 27 mins
In this episode of NeURoscience Perspectives, John J. Foxe, PhD, the director of the Del Monte Institute for Neuroscience at the University of Rochester, is joined by Yoland Smith, PhD, Division Chief, Neuropharmacology and Neurologic Diseases, Emory National Primate Research Center. Dr. Smith [https://bit.ly/43TGPwG] seeks to understand the pathophysiology of Parkinson's Disease and characterize changes in the synaptic plasticity of the basal ganglia in normal and pathological conditions. He shares one of the biggest challenges in Parkinson's research. Dr. Smith is a prolific publisher with more than 250 peer-reviewed manuscripts on the pathophysiology of brain networks in Parkinson’s disease and related movement disorders. He is also a senior editor at the European Journal of Neuroscience and discusses why it is a position he has become passionate about. He also discuss the importance of mentorship throughout ones career and why a job in academia research is the best job to have.
A transcript version is available on YouTube: https://youtu.be/mLVSTiOgOM4
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Episode Transcript
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(00:00):
On the other hand, if you sample, if we had a series of Parkinson's disease patients
(00:04):
here and you talk to them at different stages of the disease and you ask them, okay, what
is the most problematic part of your life?
What is your symptom that you really would like to get rid of?
The motor symptoms are not going to be necessarily what they will talk about.
They will talk about all other types of symptoms that they have, which can then be a broad
range of autonomic dysfunctions or cognitive dysfunctions or even later, that's why, those
(00:30):
psychiatric problems.
And when we get to that part then, when we get there, the reason why those ones are so
problematic is that we do not know the circuitry for that.
So this is where we get stuck.
The human brain is the most complex structure in the known universe and we are in the middle
of a scientific revolution to understand its inner workings.
(00:51):
Join us for a conversation with world renowned neuroscientists as they visit Rochester.
I am Dr. John Fox, Director of the Del Monte Institute for Neuroscience at the University
of Rochester and you are listening to Neuroscience Perspectives.
I'm John Fox, Director of the Del Monte Institute for Neuroscience and I'd like to welcome you
(01:12):
to another episode of Neuroscience Perspectives.
Today we're going to talk about Parkinson's disease.
Extraordinarily, 90,000 Americans will receive a new diagnosis of Parkinson's every single
year.
Today, we have a real Parkinson's expert.
My guest is Dr. Jolland Smith, who's a Professor of Neurology at Emory University School of
(01:34):
Medicine.
Jolland, welcome.
Welcome to Neuroscience Perspectives.
It's great to have you here.
Thanks.
Thanks for the invitation.
So listen, let's get stuck in here on Parkinson's and we'll come back.
I have a whole bunch of things I want to talk to you about.
I want to talk to you about your role in publishing.
You and I work in the journal together and also your path to science.
But let's dive into Parkinson's to begin with.
(01:56):
Why is there such an extraordinary increase in the number of people being diagnosed with
Parkinson's?
This is the disease of aging, right?
So I guess the issue with those disorders is that it's the same thing for Alzheimer's.
We hear a lot about Alzheimer's disease, which is really growing at a faster pace.
(02:17):
It's just essentially pretty basic, right?
We're living longer, but our brain does not follow.
That's essentially what's going on, right?
It's that we're just kind of moving and we have, obviously, we have really all good medical
treatment to keep us alive and having a long life.
But somehow the brain is degenerating at some point.
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And then depending on the people and depending, of course, there is always a composition,
a mix of predisposition for these disorders, right?
And also a component of aging.
So like predisposition, clearly there are people who might have been exposed.
We talk about Parkinson's, for instance, toxin in the environment, right?
(02:59):
The environment plays a role, of course.
It is important.
But it's not the cause, right?
I mean, there are people who can be exposed to environmental toxin for all their life
and will never get Parkinson's.
So on the other hand, if you have a predisposition to have Parkinson and you are exposed to it,
then you become, I mean...
So all of this put together really kind of create essentially an environment in which
(03:25):
that may help, you know, kind of a dense.
But I think aging is definitely the main reason why it's going so fast.
Here in Rochester, there's a center here, just like you have at Emory, a Udall Center
for Parkinson's disease, one of the NIH centers.
And there's been a real concentration on environmental toxins because right outside the city of Rochester
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is one of the green gardens of the United States.
So we have a lot of rural counties.
And there, there's a very high prevalence in the farming communities, the rural communities
of Parkinson's, probably around environmental toxins and fertilizers, I suppose, in the
70s and 80s and that.
Is that a big component?
Oh, yeah, it is.
It is definitely.
I think that has been around.
That's why you mentioned, I think, this idea has been around for quite some time now, right?
(04:11):
In fact, it has been one thing that has generated a big bump into the Parkinson, the role of
environmental toxin in Parkinson's.
And there's been this discovery in the mid-1980s of this neurotoxin that is called MPTP, right?
This neurotoxin that was found by inadvertence as a contaminant of a batch of synthetic heroin
(04:33):
that some, unfortunately, some young people from California had been taken and then ending
up overnight, essentially, in emergency rooms throughout the Bay Area in California with
severe symptoms of Parkinson's disease.
And of course, because they were very young and they did not have, they were not people
(04:56):
who should have Parkinson's disease, at least the majority.
And then the question was, what was going on, essentially?
And finally, after having been found out as elating this compound from this synthetic
heroin, all the whole story that came with that, then they realized that the synthetic
heroin like MPTP, this neurotoxin, is very similar chemically to some of these toxins
(05:20):
that we have in the environment, right?
That are very similar.
Right, right, right.
And indeed, you know-
In fertilizers and weed killers.
Yeah, yeah.
And if you expose neurons in the brain that degenerate in Parkinson, like the dopamine
cell, which is the main, you know, this is the main...
So if you expose these neurons to these neurotoxins, I mean, they're going to die.
I mean, they are very sensitive.
This is a very particular population of cell that have different properties and this has
(05:43):
been studied.
And they are very sensitive to this.
So that's why, you know, I mean, yeah, the role of memory toxin is important.
And we cannot-
And now you mentioned dopamine.
And I think, you know, the average listener or viewer would be thinking dopamine, no,
that's the reward stuff.
But it has another extraordinarily important role, right, in movement and motion and that,
(06:05):
and in very specific neural circuits.
Would you want to talk a little bit about that?
Yeah, yeah, that's right.
So dopamine, indeed, that's right.
Dopamine is, as you mentioned, is critical for reward, very important.
But that's why the component is that the dopamine is depending on where the dopamine is located.
And so there is component of the brain that are essentially regulated by dopamine, but
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these are deeply involved in movement control.
So these are different brain regions.
These are different components of brain regions.
And those ones are the ones that get affected in Parkinson's disease.
In fact, the area of the brain that really is regulated by dopamine and receive a lot
of the motor input, if you want, are the first areas that are targeted in Parkinson's disease.
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So this part of the brain gets hit.
And then the dopamine neurons that are selectively really affecting those regions of the brain
are degenerating.
The other one that when you talk about reward, those neurons really will be eventually affected,
but much later in the process.
And then you have, indeed, Parkinson is not just a motor disorder, right?
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So clearly, the motor component kicks in and you can see that and people will have some
motor deficit.
But Parkinson gets very complex and can have really definitely an emotional component,
a psychiatric component, a cognitive component.
And all of this is probably due in part to dopamine loss, but maybe dopamine loss in
other brain regions than the area that control motor.
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So then you talk about the prefrontal cortex, for instance, which is heavily involved in
various aspects of cognition and various psychiatric disorders.
So when those regions, then when those neurons that are controlling dopamine cell that are
involving reward gets affected, then people start having neuropsychiatric problems.
And for instance, impulse disorders.
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So people will start doing things that...
And hallucinations too, right?
Hallucinations, hallucinations, impulse disorders, but then really compulsive gambling.
People do think that they would...
And these are people who would have never done that before.
This is not like you are a gambler and then you just become a worse gambler, but it's
just that people start doing things that they have never done before.
Never had any interest in before.
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And that is probably related in part to dopamine, but also other type of chemicals and the chemical
changes in the brain.
Now I have a colleague here and he would say the great thing about Parkinson's disease,
you never say there's a great thing about a disease, is that the circuitry is so well
understood unlike many, many other diseases.
We can't say here are the central nodes that are going awry in schizophrenia, but in Parkinson's
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disease we know this.
And so he would say in some ways it's the most curable.
We know a lot of the causes, they're environmental, at least the precipitants.
We know the circuits and we also know the chemistry that's involved.
Do you share that?
Yeah.
I share that when you talk about moderate aspect of Parkinson's.
That is perfectly true.
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And this is why if you look about this, Parkinson in fact, if you are...
And you're right, I think, to use the term and I use that as well as well.
So I mean, if you have to get the disease, a neurodermal disorder as we get older, I
hope that I will get Parkinson and not get really Alzheimer or other type of disorder
because simply, because we have the hard good, really relative good treatment that can help
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people live with the disease, hopefully.
And that is fine as long as the disease is really largely moderate.
Okay, largely dissolved moderate.
If you have moderate symptoms, they get severe and so on, you can be taken care of.
So these are the tremors, the shuffle.
The slowness of movements, all of that.
(09:49):
That can be taken care of by different therapy, drugs, and also there is deep brain stimulation.
Well, I was going to ask you about deep brain stimulation.
Because the circuits are so well understood, you can actually put electrodes in and target
those areas.
Yeah, you can do that and that will take care of some of the moderate.
But on the other hand, if you sample, if we had a series of Parkinson disease patients
(10:12):
here and you talk to them at different stages of the disease and you ask them, okay, what
is the most problematic part of your life?
What is your symptom that you really would like to get rid of?
The moderate symptoms are not going to be necessarily what they will talk about.
They will talk about all other type of symptoms that they have, which can then be a broad
range of autonomic dysfunctions or cognitive dysfunctions or even later, that's why, those
(10:37):
psychiatric problems.
And when we get to that part then, when we get there, the reason why those ones are so
problematic is that we do not know the circuitry for that.
So this is where we get stuck.
So we are at that level, we have as limited knowledge as you mentioned, schizophrenia,
harder type of psychiatric disorders.
We are at the same level.
(11:00):
And that's why there is a lot of research now in Parkinson disease, including ours,
that we try to take advantage of our research to try to go after maybe like in our hand,
cognitive impairment, try to better understand why people with Parkinson develop some mild
and then more severe cognitive impairment.
(11:22):
So what are the circuits involved into this?
So that's an area which is growing quite a bit.
Let's switch gears.
We could talk about this all day, obviously.
But let's switch gears, you're a prolific publisher of scientific papers, more than
250 papers in the literature and counting.
We won't get into all the extraordinary well cited body of work.
(11:44):
But the other piece of the publishing world that you're involved in is one that you and
I actually work together on.
We are co-editors of one of the major journals in the field, the European Journal of Neuroscience.
And papers really are the product, they're the output of a scientist.
Just the measure of the work that you've done.
I had a mentor who used to say, if it's not published, it doesn't exist.
(12:08):
And I think that's really true, because otherwise how are people going to learn about what it
is you did?
Can we speak a little bit though about the publishing business and maybe the differences
between a society journal and maybe the more commercial journals that are out there and
where you are on that?
This involvement in the journal is definitely for me as really almost as important as my
(12:29):
research now.
I think it is really fundamental.
And there are always different reasons that you would think essentially for someone from
the outside is why would someone spend his time doing that?
What is the point of doing this?
But in fact, I would probably have asked myself the same question maybe 10 years ago, without
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having been.
But once you get involved into this, once I got involved into this more deeply and I
started interacting with you and other colleagues and so I start to also knowing the purpose
of the journal and the importance of the journal in so many levels of advancing neuroscience
but also educating the community and so on.
(13:11):
So the one thing of course about and also knowing the difference between society journal
versus other kind of journal, which are more like for-profit journals.
The society journal like EGN, the goal of these journal is really yet to publish great
science, advancing science and inform the neuroscientists about but it's also to really
to use the funds that are generated by the journal to subscription and so on to help
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so many other things in terms of education, in terms of helping underdeveloped countries
in developing and underrepresented minorities.
There are so many areas where through the federation of neuroscience society that the
journal can help.
And that's really the main mission of the journal.
Our goal here for us as society journals is first of all is to help advancing neuroscience
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and then we must be very rigorous in the kind of the data that we put out.
We cannot just, you know, but also is to help scientists to publish their work.
This is our goal.
We are there to help them and we have, you know, we have the kind of the privilege to
be at the entrance to this, you know, so that because the papers come, you know, come to
us and then we have to make a decision really how to handle this.
(14:27):
But this is, but the way that we see that is that really we will do everything we can
to try to get this paper out.
Okay.
So that's the idea and we'll work together with the authors, we'll provide the input
as much as needed, you know, to try to make it and that's our mission.
So our mission is not, you know, to go after and then see this and read the abstract and
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then decide, okay, so that's not flashy enough, you know, for us.
We're not going after that.
So this is not the goal of journal and that is, this is not what we do.
Completely different philosophy.
Completely different philosophy.
They're there to advance the science, not to go for the flashy.
Yeah, yeah, yeah.
And this is really important point is that yes, journals make money, but in the case
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of the society's journals, that money goes back into the scientific enterprise.
It doesn't go to a shareholder and so on.
And again, there's nothing, not saying there's anything necessarily wrong with the corporate
approach to these things, but an absolute distinction for the society journals is where
the profits are going.
They're going back into the community to support scholarships, workshops, the meetings like
our Federation of European Neuroscience Societies meeting, the FENS meeting and so on.
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And that's something which is not, you know, which is unfortunately really not necessarily,
people don't know as much.
If you're not involved in a journal as at the level of the editors of the journal, right,
you do not really appreciate that.
I mean, it's not like you don't have the background and the essence to make this, but this is
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pretty striking.
And I don't think, you know, in our case, EGN is not different from other society journal.
I mean, it does the same thing for FENS that other journal will do for the society, but
that's the big, and for that reason, I think it's our really, personally, I feel that it's
my response, as a PI in my lab and when come the time, you know, to publish some of my
papers and so on.
(16:17):
Definitely EGN will be there.
We need to, we take the response to try to publish some of our work on a regular basis
in EGN to help, you know, to help the journal.
As somebody who's published more than 250 papers in all the top journals in the world,
you know, your expertise, your experience, your ability to write a sensible paper, the
(16:37):
fact that you're taking those expertise and giving them back to the community through
your work as an editor, I think that it says a lot about you.
And I think it also, you'll find that across, we're talking about EGN because that's our
journal, but you'll find that across all the society journals.
It's senior scientists with a lot of expertise who are shepherding the process.
That's really, really crucial.
(16:58):
Yeah.
No, no, that's important.
That's different to something that I really cherish very much and I really feel it is
important and I definitely educate, because I think what we need to do as well is to educate
the young generation about this too.
Not only, but definitely I think this is something that can get lost and I really take responsibility
(17:19):
to try to at least talk to our students, you know, to our graduate students and organizing,
you know, just workshop to talk about this publishing, you know, what it is and where
will you send your journal?
And that's really, people can do whatever they want.
But at the end of the day, I think it's important that they have this knowledge about, you know,
and then, you know, they can, but it's important to have the background and then decide and
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that's something, you know, that's something which is really, really important.
Yeah.
Well, I'll often, you mentioned that too, have younger scientists ask me, like, why
are you devoting so much time to doing this editorial work?
And I always say, it's a little, so it's been a few years since you and I were in graduate
school, let's put it that way.
For me, doing the editorial work means that, you know, obviously you read the work in your
(18:03):
area in Parkinson's disease very, very carefully and I do that for the work that's close to
my own area of expertise.
But editing in a journal, you read everything.
You're reading across every single domain.
And for me, it's like being a permanent continuing education.
And I think it's made me a better scientist over time.
No, that's a great point.
Yeah, you kind of, yeah, you kind of learn from the, it's sort of at the same time as
(18:25):
a source, you know, of knowledge, right?
I mean, you're not just a, really, you get, you know, you get a good knowledge about neuroscience
going on in many different fields.
That's a great point, yeah.
I like it.
Let's talk about you, because I, you know, people, people who come on neuroscience perspectives,
I always want to ask them, like, where is, what was the trajectory?
And of course, you know, it'll be becoming clear to our listeners that you didn't grow
(18:47):
up in the United States of America, but you grew up in another part of the Americas.
Tell us about Quebec, where you grew up.
How did you end up in science?
And what was the trajectory, true, to land you in Atlanta as a professor at Emory University?
Yeah, yes.
That's interesting, right?
I were, I just had, really, on the lunchtime, having a meeting with the graduate students,
(19:09):
and it's talking about, you know, what, how we end up there.
So, you know, on my end, that's why.
So I think, as you mentioned, of course, I'm not from the U.S.
I'm French-Canadian.
My first language is French.
I've been spending, practically, all my life, except for the last 27.
Now, I've been in Atlanta for about 23 years now.
So but I spend all my life in Quebec, Quebec City.
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But I come, you know, my trajectory to science, so I come from a very, both my wife and I,
in fact, who have been together forever.
I mean, we come from very tiny villages on the extreme east part of the province of Quebec,
which is what we call the Gaspé-Z, which is the Gaspé area, which is along the Atlantic.
And very tiny villages, about a thousand people, you know, each next to each other.
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So I did all my high school there.
And then, of course, for these small villages, then you need to move out of that.
When come the time for college, you know, you need to get out because there's not then,
this is where, you know, I moved to Quebec City.
And then in Quebec City, there is one, one university, which is Lauderdale University,
which is a French, French university and large, you know, about 40, 50,000 students.
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So to see where we end up.
And then at that time, you know, things are maybe like many, many students, essentially.
I wasn't, I did not know, I did not have research in mind, of course, at the beginning.
It was not research was, particularly for me, not having grown in the city and everything.
Research was in the small place where we come from.
I mean, this is far away from the big center, you know, we got.
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So but on the other hand, you know, I discovered that and I remember that the click started,
you know, I was, I was in the biology, maybe major doing biology, general thing, but I
wasn't interested in human, humans.
I needed to do something related to human health.
Right.
So it was, of course, medicine is one thing you think about, okay, medical school might
be good for me.
And but then I had this course and I remember that course I took as an elective course during
(21:04):
a bachelor degree during my, I think it was my third year.
It wasn't neuroscience course.
It was just given there and I took it just because it was related to somehow understanding
the brain, right.
Human thing.
And this course has been the click that made me think about neuroscience, not, I mean,
human health then was one thing, but then neuroscience became the pillar of that.
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And, and, and then I started, then after that, I started digging a bit more about it, started
to try to know what can, what else can I get in here?
And then I realized that, okay, the next step was to try to find people who do neuroscience.
And I went to a, a, an hospital where there was a center for neuroscience research and,
and the center was very, it was a small center, but very focused on Parkinson's disease and
(21:49):
basic ganglia, which are the areas of the brain affected.
Then I, I, I, yeah, it started there, you know, and I loved it.
And I, I had a very good mentor, very, I mean, the mentors, of course, that's one thing maybe
to plug in here, which is important is that to be really for any, any, anybody, essentially
at any step of life, we need good mentoring.
(22:10):
I mean, without mentoring, we cannot, we cannot do it at any levels.
And in terms of graduate education, that's post-doc, whatever, you need good mentors.
And this has been, this has been lucky to find that and people have guided me.
And then, and then after that, did my PhD and then move.
And then I spent a couple of years in Oxford in the medical research council unit there,
(22:31):
where I get another really outstanding mentor, what became, Dr. Paul Boland, who became.
Well, we have to mention Paul, who's a former editor-in-chief of our journal, the European
Journal of Neuroscience.
I'm a very close friend of Paul.
Yeah, a very close friend and we had a good time.
And then after that, you know, I went back to Canada for about five years and, and there
was in 1996, there was this opportunity that I was, I was very, I mean, I did the post-doc
(22:54):
with, after Oxford, I did the post-doc with Maylon DeLong, who is a very well-known neurologist,
you know, in the field of Parkinson's disease.
And we talked about deep brain stimuli, he's been a pioneer in, in, in treating that.
So I went to, I went to the post-doc with Maylon and then in, in 96, you know, he had
the possibility for me to move back.
He was at that time the chair of Emory University.
(23:15):
And there was a possibility for me to move there and, and this was, you know, this was
too good to be, to be true.
So we decided to make the move and join neurology department there and the Emory Primate Center.
And yeah, and we've been there, you know, for, since then.
And this has been probably, yeah, the best decision I've made.
I think I've been, it has been a fantastic time at Emory.
(23:38):
We love, I love the Emory community.
We love the neuroscience community.
I'm very well, even if I'm not a neurologist myself, I'm very much integrated in the neurology
department.
So I have a lot of colleagues, you know, who are neurologists, you know, at different people
who do research, people who do clinical work, people who do, who do maybe more neuroscience
basic work.
And we have the way that the system is organized, we have a lot of possibility for interacting
(24:02):
and exchanging together.
And I'm also at that stage as well.
One part of this that really is, is critical for me is also teaching and mentoring, right?
I think we feel, we all feel that I'm sure as we do our research, but also the other
part is what is really rewarding for us is to be able to train the students, right, or
the postdoc and, and see them on their hand, you know, grow and become, you know, become
(24:27):
who they are, right?
Let me ask you that, and we see a lot of our PhD graduates now choosing not the academic
route, choosing to walk away from the research enterprise.
And of course, there's a big sucking sound as the big data firms, the Googles, the Facebooks,
take the PhD students that would formerly have gone down that route into their more
(24:49):
corporate world.
Are you worried about that?
And what would you say to a youngster looking at that fork in the road and saying, you know,
I could go over into this corporate world and make a lot of money, let's face it, or
should I stay in the academic track?
Is there something that we should be saying to somebody to say, look, you know, stay the
course, it's worthwhile.
(25:09):
Academic research, you know, is, is fantastic.
Who can have a better job than what we do, right?
I mean, we wake up every morning and our goal is to just to come and think about, you know,
what are the next questions we want to, so, so there's no other job that offers you this.
So if you, so that's one, so I think personally what I feel is that what I tell students is
that if you have the, if you feel that this is something critical for you and you have
(25:33):
this drive inside yourself, you don't have, you know, to come and then, oh, what do I
do today?
I don't know what I'm going.
So if you come, you know, every day and you, you get to the lab and you get, and you have
this, all this thing driving you, that means that you have something inside you that is,
you know, that is done for science, right?
That's one thing where you should, because you need to have that.
If you don't have that, probably you're not at the right place because you need that because
(25:56):
it's an, we know, we know what the cons are, right?
It's competitive.
There is a lot of people, there is a lot of very, a lot of ton of people who would want
to go after the same, you know, funding that you will be doing, but, but there is place
for you if you have that.
And then of course, after that, you know, you need to, to take this and, and take advantage
of that, take your, take your career, you need to take your career in your hands and
(26:18):
move in forward.
You know, you need to take the lead on your career and, and, and, and go with it positively
and find that you surround yourself with a good, a good team of people taking advantage
of the resources that your graduate program offers you taking, making a network, you know,
talking with people, you need to develop network.
So you need a lot of things that you need to yourself to take care of.
(26:41):
But if you do that, people will be pleased, you know, and excited to give you and train
you and help you advancing that.
But you need to take the lead on your own career and you need to have this motivation.
If you have that, there's no reason why you should not, you know, we should, you should
not succeed in this place.
There is place for you in research.
I mean, that would be my thing.
Yeah.
(27:02):
Well, I think you said it.
What better job in there in the world is there than this?
And I think that that captures it really well.
And it's obvious in you that that passion is, is alive and strong and long may it go
on.
So I think the very best of luck with the work, here's to a cure for Parkinson's in
our lifetime.
And thanks for being here with us.
OK, it's a pleasure.
(27:23):
Thanks for having me, and thanks for having me, and thanks for having me, and thanks for
On the other hand, if you sample, if we had a series of Parkinson's disease patients
(00:04):
here and you talk to them at different stages of the disease and you ask them, okay, what
is the most problematic part of your life?
What is your symptom that you really would like to get rid of?
The motor symptoms are not going to be necessarily what they will talk about.
They will talk about all other types of symptoms that they have, which can then be a broad
range of autonomic dysfunctions or cognitive dysfunctions or even later, that's why, those
(00:30):
psychiatric problems.
And when we get to that part then, when we get there, the reason why those ones are so
problematic is that we do not know the circuitry for that.
So this is where we get stuck.
The human brain is the most complex structure in the known universe and we are in the middle
of a scientific revolution to understand its inner workings.
(00:51):
Join us for a conversation with world renowned neuroscientists as they visit Rochester.
I am Dr. John Fox, Director of the Del Monte Institute for Neuroscience at the University
of Rochester and you are listening to Neuroscience Perspectives.
I'm John Fox, Director of the Del Monte Institute for Neuroscience and I'd like to welcome you
(01:12):
to another episode of Neuroscience Perspectives.
Today we're going to talk about Parkinson's disease.
Extraordinarily, 90,000 Americans will receive a new diagnosis of Parkinson's every single
year.
Today, we have a real Parkinson's expert.
My guest is Dr. Jolland Smith, who's a Professor of Neurology at Emory University School of
(01:34):
Medicine.
Jolland, welcome.
Welcome to Neuroscience Perspectives.
It's great to have you here.
Thanks.
Thanks for the invitation.
So listen, let's get stuck in here on Parkinson's and we'll come back.
I have a whole bunch of things I want to talk to you about.
I want to talk to you about your role in publishing.
You and I work in the journal together and also your path to science.
But let's dive into Parkinson's to begin with.
(01:56):
Why is there such an extraordinary increase in the number of people being diagnosed with
Parkinson's?
This is the disease of aging, right?
So I guess the issue with those disorders is that it's the same thing for Alzheimer's.
We hear a lot about Alzheimer's disease, which is really growing at a faster pace.
(02:17):
It's just essentially pretty basic, right?
We're living longer, but our brain does not follow.
That's essentially what's going on, right?
It's that we're just kind of moving and we have, obviously, we have really all good medical
treatment to keep us alive and having a long life.
But somehow the brain is degenerating at some point.
(02:39):
And then depending on the people and depending, of course, there is always a composition,
a mix of predisposition for these disorders, right?
And also a component of aging.
So like predisposition, clearly there are people who might have been exposed.
We talk about Parkinson's, for instance, toxin in the environment, right?
(02:59):
The environment plays a role, of course.
It is important.
But it's not the cause, right?
I mean, there are people who can be exposed to environmental toxin for all their life
and will never get Parkinson's.
So on the other hand, if you have a predisposition to have Parkinson and you are exposed to it,
then you become, I mean...
So all of this put together really kind of create essentially an environment in which
(03:25):
that may help, you know, kind of a dense.
But I think aging is definitely the main reason why it's going so fast.
Here in Rochester, there's a center here, just like you have at Emory, a Udall Center
for Parkinson's disease, one of the NIH centers.
And there's been a real concentration on environmental toxins because right outside the city of Rochester
(03:46):
is one of the green gardens of the United States.
So we have a lot of rural counties.
And there, there's a very high prevalence in the farming communities, the rural communities
of Parkinson's, probably around environmental toxins and fertilizers, I suppose, in the
70s and 80s and that.
Is that a big component?
Oh, yeah, it is.
It is definitely.
I think that has been around.
That's why you mentioned, I think, this idea has been around for quite some time now, right?
(04:11):
In fact, it has been one thing that has generated a big bump into the Parkinson, the role of
environmental toxin in Parkinson's.
And there's been this discovery in the mid-1980s of this neurotoxin that is called MPTP, right?
This neurotoxin that was found by inadvertence as a contaminant of a batch of synthetic heroin
(04:33):
that some, unfortunately, some young people from California had been taken and then ending
up overnight, essentially, in emergency rooms throughout the Bay Area in California with
severe symptoms of Parkinson's disease.
And of course, because they were very young and they did not have, they were not people
(04:56):
who should have Parkinson's disease, at least the majority.
And then the question was, what was going on, essentially?
And finally, after having been found out as elating this compound from this synthetic
heroin, all the whole story that came with that, then they realized that the synthetic
heroin like MPTP, this neurotoxin, is very similar chemically to some of these toxins
(05:20):
that we have in the environment, right?
That are very similar.
Right, right, right.
And indeed, you know-
In fertilizers and weed killers.
Yeah, yeah.
And if you expose neurons in the brain that degenerate in Parkinson, like the dopamine
cell, which is the main, you know, this is the main...
So if you expose these neurons to these neurotoxins, I mean, they're going to die.
I mean, they are very sensitive.
This is a very particular population of cell that have different properties and this has
(05:43):
been studied.
And they are very sensitive to this.
So that's why, you know, I mean, yeah, the role of memory toxin is important.
And we cannot-
And now you mentioned dopamine.
And I think, you know, the average listener or viewer would be thinking dopamine, no,
that's the reward stuff.
But it has another extraordinarily important role, right, in movement and motion and that,
(06:05):
and in very specific neural circuits.
Would you want to talk a little bit about that?
Yeah, yeah, that's right.
So dopamine, indeed, that's right.
Dopamine is, as you mentioned, is critical for reward, very important.
But that's why the component is that the dopamine is depending on where the dopamine is located.
And so there is component of the brain that are essentially regulated by dopamine, but
(06:26):
these are deeply involved in movement control.
So these are different brain regions.
These are different components of brain regions.
And those ones are the ones that get affected in Parkinson's disease.
In fact, the area of the brain that really is regulated by dopamine and receive a lot
of the motor input, if you want, are the first areas that are targeted in Parkinson's disease.
(06:52):
So this part of the brain gets hit.
And then the dopamine neurons that are selectively really affecting those regions of the brain
are degenerating.
The other one that when you talk about reward, those neurons really will be eventually affected,
but much later in the process.
And then you have, indeed, Parkinson is not just a motor disorder, right?
(07:15):
So clearly, the motor component kicks in and you can see that and people will have some
motor deficit.
But Parkinson gets very complex and can have really definitely an emotional component,
a psychiatric component, a cognitive component.
And all of this is probably due in part to dopamine loss, but maybe dopamine loss in
other brain regions than the area that control motor.
(07:37):
So then you talk about the prefrontal cortex, for instance, which is heavily involved in
various aspects of cognition and various psychiatric disorders.
So when those regions, then when those neurons that are controlling dopamine cell that are
involving reward gets affected, then people start having neuropsychiatric problems.
And for instance, impulse disorders.
(07:58):
So people will start doing things that...
And hallucinations too, right?
Hallucinations, hallucinations, impulse disorders, but then really compulsive gambling.
People do think that they would...
And these are people who would have never done that before.
This is not like you are a gambler and then you just become a worse gambler, but it's
just that people start doing things that they have never done before.
Never had any interest in before.
(08:19):
And that is probably related in part to dopamine, but also other type of chemicals and the chemical
changes in the brain.
Now I have a colleague here and he would say the great thing about Parkinson's disease,
you never say there's a great thing about a disease, is that the circuitry is so well
understood unlike many, many other diseases.
We can't say here are the central nodes that are going awry in schizophrenia, but in Parkinson's
(08:44):
disease we know this.
And so he would say in some ways it's the most curable.
We know a lot of the causes, they're environmental, at least the precipitants.
We know the circuits and we also know the chemistry that's involved.
Do you share that?
Yeah.
I share that when you talk about moderate aspect of Parkinson's.
That is perfectly true.
(09:05):
And this is why if you look about this, Parkinson in fact, if you are...
And you're right, I think, to use the term and I use that as well as well.
So I mean, if you have to get the disease, a neurodermal disorder as we get older, I
hope that I will get Parkinson and not get really Alzheimer or other type of disorder
because simply, because we have the hard good, really relative good treatment that can help
(09:27):
people live with the disease, hopefully.
And that is fine as long as the disease is really largely moderate.
Okay, largely dissolved moderate.
If you have moderate symptoms, they get severe and so on, you can be taken care of.
So these are the tremors, the shuffle.
The slowness of movements, all of that.
(09:49):
That can be taken care of by different therapy, drugs, and also there is deep brain stimulation.
Well, I was going to ask you about deep brain stimulation.
Because the circuits are so well understood, you can actually put electrodes in and target
those areas.
Yeah, you can do that and that will take care of some of the moderate.
But on the other hand, if you sample, if we had a series of Parkinson disease patients
(10:12):
here and you talk to them at different stages of the disease and you ask them, okay, what
is the most problematic part of your life?
What is your symptom that you really would like to get rid of?
The moderate symptoms are not going to be necessarily what they will talk about.
They will talk about all other type of symptoms that they have, which can then be a broad
range of autonomic dysfunctions or cognitive dysfunctions or even later, that's why, those
(10:37):
psychiatric problems.
And when we get to that part then, when we get there, the reason why those ones are so
problematic is that we do not know the circuitry for that.
So this is where we get stuck.
So we are at that level, we have as limited knowledge as you mentioned, schizophrenia,
harder type of psychiatric disorders.
We are at the same level.
(11:00):
And that's why there is a lot of research now in Parkinson disease, including ours,
that we try to take advantage of our research to try to go after maybe like in our hand,
cognitive impairment, try to better understand why people with Parkinson develop some mild
and then more severe cognitive impairment.
(11:22):
So what are the circuits involved into this?
So that's an area which is growing quite a bit.
Let's switch gears.
We could talk about this all day, obviously.
But let's switch gears, you're a prolific publisher of scientific papers, more than
250 papers in the literature and counting.
We won't get into all the extraordinary well cited body of work.
(11:44):
But the other piece of the publishing world that you're involved in is one that you and
I actually work together on.
We are co-editors of one of the major journals in the field, the European Journal of Neuroscience.
And papers really are the product, they're the output of a scientist.
Just the measure of the work that you've done.
I had a mentor who used to say, if it's not published, it doesn't exist.
(12:08):
And I think that's really true, because otherwise how are people going to learn about what it
is you did?
Can we speak a little bit though about the publishing business and maybe the differences
between a society journal and maybe the more commercial journals that are out there and
where you are on that?
This involvement in the journal is definitely for me as really almost as important as my
(12:29):
research now.
I think it is really fundamental.
And there are always different reasons that you would think essentially for someone from
the outside is why would someone spend his time doing that?
What is the point of doing this?
But in fact, I would probably have asked myself the same question maybe 10 years ago, without
(12:49):
having been.
But once you get involved into this, once I got involved into this more deeply and I
started interacting with you and other colleagues and so I start to also knowing the purpose
of the journal and the importance of the journal in so many levels of advancing neuroscience
but also educating the community and so on.
(13:11):
So the one thing of course about and also knowing the difference between society journal
versus other kind of journal, which are more like for-profit journals.
The society journal like EGN, the goal of these journal is really yet to publish great
science, advancing science and inform the neuroscientists about but it's also to really
to use the funds that are generated by the journal to subscription and so on to help
(13:39):
so many other things in terms of education, in terms of helping underdeveloped countries
in developing and underrepresented minorities.
There are so many areas where through the federation of neuroscience society that the
journal can help.
And that's really the main mission of the journal.
Our goal here for us as society journals is first of all is to help advancing neuroscience
(14:06):
and then we must be very rigorous in the kind of the data that we put out.
We cannot just, you know, but also is to help scientists to publish their work.
This is our goal.
We are there to help them and we have, you know, we have the kind of the privilege to
be at the entrance to this, you know, so that because the papers come, you know, come to
us and then we have to make a decision really how to handle this.
(14:27):
But this is, but the way that we see that is that really we will do everything we can
to try to get this paper out.
Okay.
So that's the idea and we'll work together with the authors, we'll provide the input
as much as needed, you know, to try to make it and that's our mission.
So our mission is not, you know, to go after and then see this and read the abstract and
(14:51):
then decide, okay, so that's not flashy enough, you know, for us.
We're not going after that.
So this is not the goal of journal and that is, this is not what we do.
Completely different philosophy.
Completely different philosophy.
They're there to advance the science, not to go for the flashy.
Yeah, yeah, yeah.
And this is really important point is that yes, journals make money, but in the case
(15:13):
of the society's journals, that money goes back into the scientific enterprise.
It doesn't go to a shareholder and so on.
And again, there's nothing, not saying there's anything necessarily wrong with the corporate
approach to these things, but an absolute distinction for the society journals is where
the profits are going.
They're going back into the community to support scholarships, workshops, the meetings like
our Federation of European Neuroscience Societies meeting, the FENS meeting and so on.
(15:37):
And that's something which is not, you know, which is unfortunately really not necessarily,
people don't know as much.
If you're not involved in a journal as at the level of the editors of the journal, right,
you do not really appreciate that.
I mean, it's not like you don't have the background and the essence to make this, but this is
(15:57):
pretty striking.
And I don't think, you know, in our case, EGN is not different from other society journal.
I mean, it does the same thing for FENS that other journal will do for the society, but
that's the big, and for that reason, I think it's our really, personally, I feel that it's
my response, as a PI in my lab and when come the time, you know, to publish some of my
papers and so on.
(16:17):
Definitely EGN will be there.
We need to, we take the response to try to publish some of our work on a regular basis
in EGN to help, you know, to help the journal.
As somebody who's published more than 250 papers in all the top journals in the world,
you know, your expertise, your experience, your ability to write a sensible paper, the
(16:37):
fact that you're taking those expertise and giving them back to the community through
your work as an editor, I think that it says a lot about you.
And I think it also, you'll find that across, we're talking about EGN because that's our
journal, but you'll find that across all the society journals.
It's senior scientists with a lot of expertise who are shepherding the process.
That's really, really crucial.
(16:58):
Yeah.
No, no, that's important.
That's different to something that I really cherish very much and I really feel it is
important and I definitely educate, because I think what we need to do as well is to educate
the young generation about this too.
Not only, but definitely I think this is something that can get lost and I really take responsibility
(17:19):
to try to at least talk to our students, you know, to our graduate students and organizing,
you know, just workshop to talk about this publishing, you know, what it is and where
will you send your journal?
And that's really, people can do whatever they want.
But at the end of the day, I think it's important that they have this knowledge about, you know,
and then, you know, they can, but it's important to have the background and then decide and
(17:42):
that's something, you know, that's something which is really, really important.
Yeah.
Well, I'll often, you mentioned that too, have younger scientists ask me, like, why
are you devoting so much time to doing this editorial work?
And I always say, it's a little, so it's been a few years since you and I were in graduate
school, let's put it that way.
For me, doing the editorial work means that, you know, obviously you read the work in your
(18:03):
area in Parkinson's disease very, very carefully and I do that for the work that's close to
my own area of expertise.
But editing in a journal, you read everything.
You're reading across every single domain.
And for me, it's like being a permanent continuing education.
And I think it's made me a better scientist over time.
No, that's a great point.
Yeah, you kind of, yeah, you kind of learn from the, it's sort of at the same time as
(18:25):
a source, you know, of knowledge, right?
I mean, you're not just a, really, you get, you know, you get a good knowledge about neuroscience
going on in many different fields.
That's a great point, yeah.
I like it.
Let's talk about you, because I, you know, people, people who come on neuroscience perspectives,
I always want to ask them, like, where is, what was the trajectory?
And of course, you know, it'll be becoming clear to our listeners that you didn't grow
(18:47):
up in the United States of America, but you grew up in another part of the Americas.
Tell us about Quebec, where you grew up.
How did you end up in science?
And what was the trajectory, true, to land you in Atlanta as a professor at Emory University?
Yeah, yes.
That's interesting, right?
I were, I just had, really, on the lunchtime, having a meeting with the graduate students,
(19:09):
and it's talking about, you know, what, how we end up there.
So, you know, on my end, that's why.
So I think, as you mentioned, of course, I'm not from the U.S.
I'm French-Canadian.
My first language is French.
I've been spending, practically, all my life, except for the last 27.
Now, I've been in Atlanta for about 23 years now.
So but I spend all my life in Quebec, Quebec City.
(19:32):
But I come, you know, my trajectory to science, so I come from a very, both my wife and I,
in fact, who have been together forever.
I mean, we come from very tiny villages on the extreme east part of the province of Quebec,
which is what we call the Gaspé-Z, which is the Gaspé area, which is along the Atlantic.
And very tiny villages, about a thousand people, you know, each next to each other.
(19:53):
So I did all my high school there.
And then, of course, for these small villages, then you need to move out of that.
When come the time for college, you know, you need to get out because there's not then,
this is where, you know, I moved to Quebec City.
And then in Quebec City, there is one, one university, which is Lauderdale University,
which is a French, French university and large, you know, about 40, 50,000 students.
(20:17):
So to see where we end up.
And then at that time, you know, things are maybe like many, many students, essentially.
I wasn't, I did not know, I did not have research in mind, of course, at the beginning.
It was not research was, particularly for me, not having grown in the city and everything.
Research was in the small place where we come from.
I mean, this is far away from the big center, you know, we got.
(20:39):
So but on the other hand, you know, I discovered that and I remember that the click started,
you know, I was, I was in the biology, maybe major doing biology, general thing, but I
wasn't interested in human, humans.
I needed to do something related to human health.
Right.
So it was, of course, medicine is one thing you think about, okay, medical school might
be good for me.
And but then I had this course and I remember that course I took as an elective course during
(21:04):
a bachelor degree during my, I think it was my third year.
It wasn't neuroscience course.
It was just given there and I took it just because it was related to somehow understanding
the brain, right.
Human thing.
And this course has been the click that made me think about neuroscience, not, I mean,
human health then was one thing, but then neuroscience became the pillar of that.
(21:25):
And, and, and then I started, then after that, I started digging a bit more about it, started
to try to know what can, what else can I get in here?
And then I realized that, okay, the next step was to try to find people who do neuroscience.
And I went to a, a, an hospital where there was a center for neuroscience research and,
and the center was very, it was a small center, but very focused on Parkinson's disease and
(21:49):
basic ganglia, which are the areas of the brain affected.
Then I, I, I, yeah, it started there, you know, and I loved it.
And I, I had a very good mentor, very, I mean, the mentors, of course, that's one thing maybe
to plug in here, which is important is that to be really for any, any, anybody, essentially
at any step of life, we need good mentoring.
(22:10):
I mean, without mentoring, we cannot, we cannot do it at any levels.
And in terms of graduate education, that's post-doc, whatever, you need good mentors.
And this has been, this has been lucky to find that and people have guided me.
And then, and then after that, did my PhD and then move.
And then I spent a couple of years in Oxford in the medical research council unit there,
(22:31):
where I get another really outstanding mentor, what became, Dr. Paul Boland, who became.
Well, we have to mention Paul, who's a former editor-in-chief of our journal, the European
Journal of Neuroscience.
I'm a very close friend of Paul.
Yeah, a very close friend and we had a good time.
And then after that, you know, I went back to Canada for about five years and, and there
was in 1996, there was this opportunity that I was, I was very, I mean, I did the post-doc
(22:54):
with, after Oxford, I did the post-doc with Maylon DeLong, who is a very well-known neurologist,
you know, in the field of Parkinson's disease.
And we talked about deep brain stimuli, he's been a pioneer in, in, in treating that.
So I went to, I went to the post-doc with Maylon and then in, in 96, you know, he had
the possibility for me to move back.
He was at that time the chair of Emory University.
(23:15):
And there was a possibility for me to move there and, and this was, you know, this was
too good to be, to be true.
So we decided to make the move and join neurology department there and the Emory Primate Center.
And yeah, and we've been there, you know, for, since then.
And this has been probably, yeah, the best decision I've made.
I think I've been, it has been a fantastic time at Emory.
(23:38):
We love, I love the Emory community.
We love the neuroscience community.
I'm very well, even if I'm not a neurologist myself, I'm very much integrated in the neurology
department.
So I have a lot of colleagues, you know, who are neurologists, you know, at different people
who do research, people who do clinical work, people who do, who do maybe more neuroscience
basic work.
And we have the way that the system is organized, we have a lot of possibility for interacting
(24:02):
and exchanging together.
And I'm also at that stage as well.
One part of this that really is, is critical for me is also teaching and mentoring, right?
I think we feel, we all feel that I'm sure as we do our research, but also the other
part is what is really rewarding for us is to be able to train the students, right, or
the postdoc and, and see them on their hand, you know, grow and become, you know, become
(24:27):
who they are, right?
Let me ask you that, and we see a lot of our PhD graduates now choosing not the academic
route, choosing to walk away from the research enterprise.
And of course, there's a big sucking sound as the big data firms, the Googles, the Facebooks,
take the PhD students that would formerly have gone down that route into their more
(24:49):
corporate world.
Are you worried about that?
And what would you say to a youngster looking at that fork in the road and saying, you know,
I could go over into this corporate world and make a lot of money, let's face it, or
should I stay in the academic track?
Is there something that we should be saying to somebody to say, look, you know, stay the
course, it's worthwhile.
(25:09):
Academic research, you know, is, is fantastic.
Who can have a better job than what we do, right?
I mean, we wake up every morning and our goal is to just to come and think about, you know,
what are the next questions we want to, so, so there's no other job that offers you this.
So if you, so that's one, so I think personally what I feel is that what I tell students is
that if you have the, if you feel that this is something critical for you and you have
(25:33):
this drive inside yourself, you don't have, you know, to come and then, oh, what do I
do today?
I don't know what I'm going.
So if you come, you know, every day and you, you get to the lab and you get, and you have
this, all this thing driving you, that means that you have something inside you that is,
you know, that is done for science, right?
That's one thing where you should, because you need to have that.
If you don't have that, probably you're not at the right place because you need that because
(25:56):
it's an, we know, we know what the cons are, right?
It's competitive.
There is a lot of people, there is a lot of very, a lot of ton of people who would want
to go after the same, you know, funding that you will be doing, but, but there is place
for you if you have that.
And then of course, after that, you know, you need to, to take this and, and take advantage
of that, take your, take your career, you need to take your career in your hands and
(26:18):
move in forward.
You know, you need to take the lead on your career and, and, and, and go with it positively
and find that you surround yourself with a good, a good team of people taking advantage
of the resources that your graduate program offers you taking, making a network, you know,
talking with people, you need to develop network.
So you need a lot of things that you need to yourself to take care of.
(26:41):
But if you do that, people will be pleased, you know, and excited to give you and train
you and help you advancing that.
But you need to take the lead on your own career and you need to have this motivation.
If you have that, there's no reason why you should not, you know, we should, you should
not succeed in this place.
There is place for you in research.
I mean, that would be my thing.
Yeah.
(27:02):
Well, I think you said it.
What better job in there in the world is there than this?
And I think that that captures it really well.
And it's obvious in you that that passion is, is alive and strong and long may it go
on.
So I think the very best of luck with the work, here's to a cure for Parkinson's in
our lifetime.
And thanks for being here with us.
OK, it's a pleasure.
(27:23):
Thanks for having me, and thanks for having me, and thanks for having me, and thanks for
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