Interview with Dr. Simon Chen

📷 Dr. Simon Chen

Journalist: Amy Stewart

AMY: Hello and welcome back to SciSection. I’m your journalist, Amy Stewart, for the SciSection radio show broadcasted on CFMU 93.3 FM radio station. We are here today with Dr. Simon Chen, a professor at the University of Ottawa and a renowned researcher of the motor cortex and memory encoding. Thank you so much for joining us today Dr. Chen!

DR. CHEN: Thank you for inviting me.

AMY: Alright, so for our first question, can you give us a little background of your educational and career history?

DR. CHEN: Yes, so I did my undergrad and Phd at the University of British Columbia and finished my Phd in 2012. And after that I moved to UC San Diego, in California, to continue my post-doctoral research, and I was there for 4 years before I got an assistant professor position here at uOttawa. And so my training has always been neurobiology. My undergrad degree was in cell biology with a focus in neuroscience, and then I got my Phd in neuroscience, my post doctoral training is in neuroscience as well.

AMY: Very cool, well we're happy to hear you landed back in Canada, that's great that you are here in Ottawa now. So for my next question, what kind of research do you do in your lab regarding the motor cortex and what are some of your most significant findings thus far?

DR. CHEN: So in our lab the main question we want to study is: how does the brain acquire and maintain new motor skills. So I always like to describe to people that one day when you and I want to go play golf or play tennis, you know we know how to hold a golf club or tennis racket but to be able to serve or go really far and very straight, that's a new motor skill we’re acquiring. And then so, motor memory is very different than other forms of memory such as reward or fear. In those forms of memory. you get it really fast. When you eat something you really like or you get scared, you remember that very well, but then over a long time if you don't experience that feeling you might forget. Motor learning is very different. Motorlearning, it takes many, many practices but once you get good at it, you’d forget. So if you haven’t skied for many years and now you go to Mont-Tremblant, you still remember how to ski, so that means the brain must have acquired the fear and the reward memory different then how we acquire motor memory. And so what we want to study is, how does the brain acquire motor memory over such a long period of time. And so since I started my lab here at uottawa, I would say we have two very significant findings. With the first one, that was just released and published in UROM where we found the motor cortex,

there is a group of inhibitory neurons that sort of act like a break to choose and fine tune the motor cortex of which motor movements is the best for the motor skill you’re learning.

So let's say when we first start playing golf you might hit the ball in 10 different ways or 100 different ways, and then there must be some kind of mechanism that helps your brain to narrow down to the movement that will help you to hit the ball very far. So we found a group of inhibitory neurons in the brain that’s involved in helping the brain to fine tune down to the movement that is simple for you and then you become very stereotyped for that movement. So that’s the first major finding in my mind. And then the second one that we found is actually in a mouse disease model, specifically autism spectrum disorders. So normally children with autism spectrum disorders, they tend to have slower motor skill development, in that they learn how to play throw and catch, or other motor skills involved, games, compared to normal kids. And then that also affects their daily life because they may not be confident to play with other kids when they learn very slowly. And so what we found is that there is actually a deficit in the motor cortex and that it is contributed by this neuromodulator system called noradrenaline or norepinephrine. So we found in this specific mouse model of autism called 16p11.2 microdeletion, which is also found in human patients, that the mice, they also show a delay in motor learning and then what we found is actually due to less of these noradrenaline release to the motor cortex.

So when we use a specific manipulation to stimulate noradrenaline release in these mouse models with 16p11.2 deletions, we can actually reverse the delayed motor learning. So now these mice learn as good as the wild type.

Yeah so I would say in the past six years there are probably the two most interesting finds from my lab.

AMY: Wow those are both fascinating, I mean what you said about that group of inhibitory neurons that, like you said, fine tune the system when you learn a new skill. I mean it makes a lot of sense, I recently just started playing golf, and I find I'm terrible at it, every time I swing differently, I've only played like a handful of times but you can see how that kind of goes along with “practice makes perfect” the longer you go it’s your brain actually fine tuning and people always use the term muscle memory but I guess it's a lot less memory more neuron memory.

DR. CHEN: And the muscle memory comes when you fine tune to a specific. So I was talking to other professors the other day and there are bad habits that are also inherited. So let's say if you play golf and then you never bend your knees and eventually you have this bad habit. That bad habit’s motor memory too, right. So the ine tune doesn't just do the good things, the fine tune also will do the bad things. So once you fine tune your bad habits then that becomes a lot of muscle memory that is hard to reverse.

AMY: That is a very good point. I didn’t think about it that way. It definitely has the reverse effect and as well the reach that you've done in diseased models in mice in regarding autism I would have never imagined. It seemed so simple in terms of what you found I’m sure it took alot of work. To just realize it has to do with a deficit, is it a hormone - norepinephrine

DR. CHEN: It is a neuromodulator.

AMY: Wow yeah that as very fascinating. So for my next question can you explain what neuronal plasticity is and the role that it has in the motor cortex?

DR. CHEN: So neural plasticity actually we probably just touched upon already. So neural plasticity refers to a term that the brain is plastic. So I think for a very long time, before the 80s people think the brain, once it;s wired, it is what it is. And then people would say if I have that many brain cells, if they die then you lose your functions of the brain. And then starting the 80s, people started finding that the brain is actually plastic. It can be shaped based on experience. And then so this idea became more and more studied and people thought ok learning changes the brain connections, experience changes the brain connections, and then so that brings to the motor cortex when we say the brain’s fine tuned. That's also plasticity, right. So it's not like so if we say the brain is hardwired so that means when we are born, we are born with 100 movements. And we just routinely use these 100 movements in our daily life. But that's not the case, so we learned that we can learn a new motor skill, new motor movements and then you can fine tune into a stereotype movement that we usually do. So that's neuroplasticity, it's the brain is plastic, to be changed.

AMY: Seems like a pretty important underlying concept in the work that you do. For my next question, what are some potential applications of your findings and how can they help revolutionize our understanding of certain brain diseases and just the motor cortex in general?

DR. CHEN: So in my lab, I would say still more a basic neuroscience lab that tries to find a mechanism that happens in normal brains or in the diseased brains. But the implications can be, for example for this inhibitory neurons that I was telling you about, that you can imagine when people have a stroke and then they lose their ability to do the movement that they used to do, and then so when they go the rehabilitation and try to relearn that movement, if we know specifically which group of this inhibitory neurons are involved then perhaps we can find a way to stimulate them or inhibit them or inhibit the others so we can help the fine tune process to be faster. Because we know these inhibitory neurons can facilitate the learning process, which is also the rehabilitation process when people have a stroke. And then in the autism spectrum disorders we think with our identification of this function of this noradrenaline we can also try to find drugs that are approved by the FDA and then apply them in mice to see whether a systematic injection or drugs that cen boost up noradrenaline functions whether that can help kids with autism to improve their motor skill developments, without having any side effects. Although in my lab we don’t directly test this, that would be the implications that other researchers when they read our papers, they can apply to their work.

AMY: Yeah very much, it's fascinating to know that you pioneered all these concepts that could have great potential medical applications. I mean there are so many people out there who are suffering from strokes and different neurodegenerative diseases, as well as autism spectrum disorders. It's pretty cool to see you pioneered the work that could set up new treatments for these people. And my next question is: you used a lot of different techniques when you are researching in your lab. I was curious what are some different methodologies you used to investigate?

DR. CHEN: So the core technique in my lab - and that was one major reason I was hired at uOttawa - is we have the technique called: in vivo two proton imaging. And so basically it's a very fancy microscope that pumps a laser into the brain and so we can actually visualize the mouse’s brain at neuronal level, which is about 20 microns, or subcellular at 2 microns in the brain. And so basically when the mouse, we do a neurosurgeon surgery to the mouse so we do a craniotomy on the head and then once they’re recovered from surgery they basically have this permanent glass window that is intended right about the motor cortex. And so when you apply this microscope on top of that window you can actually visualize live neuronal cells in live animals. And then so basically compared to what people usually know about in vivo imaging like fMRI in human patients or in animals, about one box of those fMRIs we can probably identify a few 100 neurons inside that box. So basically what every we see for fMRI is that one square of signal is actually a summation of 100s of brain neurons activated. So when you can probe those hundreds of neuron activities and it give you more power to understand how does the brain work.

AMY: That is such a fascinating technique, how long have you been working on that in your career? Is this pretty recent?

So I learned that when I was a post-doc at UCSD so since 2012 but I’ve been using this two proton microscopes since I was a Phd student, yeah.

AMY: That is very cool, I'm sure it's a very helpful tool that sounds pretty neat. Ok so for my last question I wanted to know, you are a very successful researcher and I wanted to know if you had to give some advice to students who want to pursue medical research, what would you say to them?

DR. CHEN: I would say to those students who want to pursue a career in medical or science is:

chase the question you like and you're interested in but don’t chase it because “I want to cure a disease”.

Ok, because a lot of students they come in, maybe they want to go to med school, maybe they have relatives with diseases they want to cure, but then that usually frustrates them because the question is too big. And so they feel “whatever I do, I’m just moving a tiny bit in the field or I might not even contribute to that field”. But they don’t understand is that if you're just interested in this question, eventually what you find and what you study will contribute to your field. Like I just told you earlier, the things that we think we find very interesting and important, someone might use that information and apply it to clinical studies.

So as a scientist you should pursue the career just because you're curious and interested in finding the answer to the question but don’t set your goal too big or too much because you'll be frustrated along the way.

AMY: That is some very good advice. And I think you make a very good example of that as well because you’re not chasing after a specific disease or curing specific disease but because of the work you're doing your setting path for people to build off of that and because science is so connected whatever discoveries they make based of your research, you had a very big role in that,

DR. CHEN: And also one step at a time, so maybe after 30 years I'm in the field then my small steps and then one day I might collaborate with people and start doing clinical work. But you cannot jump right away, right for undergrad or from first year graduate students.

AMY: Thank you so much this was a wonderful interview, it was so facianting ot hear all the work you've been doing at uOtawa. I can wait to see what you guys get up to in your lab in the future.

DR. CHEN: Thank you for having me.

AMY: Thank you so much for coming in today Dr. Chen. That's it for this week of SciSection. I’m you host Amy Stewart and make sure to check out our podcast available on global platforms and our website, Humans and Science for our latest interviews.