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Alumni Profile

Being flexible: PhD alum Michele Insanally studies plasticity and learning in the auditory system

By April 30, 2021October 6th, 2021No Comments

“In terms of the science, the possibilities are endless. As far as I’m concerned, it’s a truly rare opportunity to study whatever questions fascinate me and make some interesting discoveries. What can be better than that?”

Michele Insanally, Neuroscience PhD Program alum (entering class of 2006)

Michele Insanally

Michele Insanally is an Assistant Professor in the Department of Otolaryngology at the University of Pittsburgh School of Medicine, where she studies flexibility in the neural circuits of the auditory system, with a focus on how we learn to interpret sounds. She uses a wide variety of experimental and computational methods in her research — an approach that she says was significantly influenced by her experiences as a graduate student in the Berkeley Neuroscience PhD Program.

Despite winning her middle school science fair with a neuroscience project, Insanally didn’t consider becoming a scientist until after graduating from Columbia University with a BA in biological sciences. She had intended to pursue medicine, but discovered her passion for research while working in a neuroscience lab after college.

At Berkeley, Insanally studied plasticity in the auditory system during early life in the lab of Shaowen Bao, who is now at the University of Arizona. She went on to do a postdoc at New York University, where she expanded her research into auditory perception and behavior. Insanally began her faculty position at the University of Pittsburgh in June 2020, and her research interests include understanding how people learn to use cochlear implants and how the tuning of these devices might be improved with feedback from neural signals.

Read our Q&A with Insanally to learn about her research, how she made decisions along her career path, and how the Berkeley Neuroscience PhD Program helped shape her as a scientist. This Q&A has been edited for length and clarity.

Q: How did you first become interested in neuroscience?

A: I was born in Guyana, which is a very small country in South America, but I grew up in New York City. I come from a family of diplomats, attorneys, and judges and I thought I would become an attorney like my father. I even went to a high school with a specialized law program (Benjamin Cardozo High School in Bayside, Queens) and I took classes like tort law. But my school also had a fantastic specialized math and science program. So in addition to taking specialized law classes, I also received a solid STEM education, and took AP Psychology and AP Calculus. Funnily enough, I actively avoided taking AP Biology because I heard it was just a rote memorization class, although I would eventually end up majoring in biology in college.

I stayed in New York City for my bachelor’s degree. I was a bio major at Columbia, but I also really loved math and physics, so I actually thought about majoring in physics. But when I looked around the department and saw that it was mostly male, it made me feel really awkward and I didn’t pursue it. My Calculus II professor tried to convince me to become a math major, but I really didn’t see the value in that at the time — which, I know sounds really crazy. But I loved biology and studying complex systems, and the people in the department were very friendly, so I chose that as my major. In those days, most good little bio majors went to medical school, and I liked the idea of helping people. So I was on the pre-med track for a while, and had this vague notion that I would go to medical school. But my heart really wasn’t in it; I was just sort of going through the motions.

Up until this point, I had not considered science or becoming a scientist. These were the days when science wasn’t in the public sphere the way it is today. [But] looking back at my childhood, I [think] I was actually always a scientist. I spent a lot of time exploring nature, turning over rocks after rain to study all the different insects that lived in my mom’s vegetable garden, catching bugs, and bird watching through my mini binoculars. I even won my middle school science fair, and my project was neuroscience related. So I was actually a young neuroscientist in the making, but I didn’t see myself as one [laughs]. That was actually my first neuroscience experiment, [and] if I can remember correctly, I was trying to determine whether our sense of smell or our sense of taste was more accurate. Sensory stuff — which is what I do now, I’m a sensory physiologist — but I was already studying sensory systems when I was in middle school! [laughs]

But after I graduated from college, I had no idea what I wanted to do. I lived in Costa Rica for a while, teaching English, having no idea what I was going to do after I got back to the States. While I was in Costa Rica, I got this email from my dean. It was a job ad for a research position at this lab at Columbia that was studying neurogenesis and stress — how neurogenesis affected cognition and what role stress played in the production of new neurons in the hippocampus. I thought this sounded so fascinating, but I didn’t really know anything about neurons. I phoned my college adviser in New York, and I told her, ‘I really want this gig, but I don’t know anything about neurons.’ She said, very matter-of-factly, ‘Michele, of course you do. A neuron is just a specialized cell.’ And then I thought, ‘Oh right! I got this!’

So I get back to New York City, I interview, and I get this position working with Tarique Perera in collaboration with Andre Fenton who was at SUNY Downstate at the time. I’m so excited. I’m working with all these other lab techs, and we’re running this really interesting spatial navigation task on rats that are really stressed out to see how they perform. And I’m all in. I spent tons of time acquainting myself with the literature on stress paradigms and hippocampal neurogenesis, and I know all of Rene Hen’s work inside and out. I was allowed to watch as the postdocs were recording [from] hippocampal place cells, and I thought it was the coolest thing ever because they would listen to the neurons ‘pop’. When neurons fire an action potential, you can hear them pop with an audio monitor —you can actually listen to this stream of neurons firing. From that moment, I knew I wanted to learn electrophysiology.

All this time, I’m supposed to be studying for my MCAT and working on my med school applications; which I have a lot of difficulty motivating myself to do, because all I want to do is research. This continues for a few months, and then my adviser Andre Fenton turns to me and says, ‘You know, you’ve really taken ownership over this project. Have you thought about going to graduate school?’ These words just struck me like a bolt of lightning. I thought to myself, of course, this makes total sense, no idea why it didn’t occur to me before. At that point, I’m tired of living in New York City and I wanted out, so I applied to graduate schools all over the country, save for anywhere in New York. And somehow I get into Cal [Berkeley], my top choice.

Q: Why was Berkeley’s Neuroscience PhD Program your top choice?

A: So many reasons why. I was applying to [schools] where I’m sure I would have received great training as a graduate student because they were all really good programs, but I decided to do it at Cal because of two things. First of all, the students seemed really happy and I thought that was going to be a predictor of my future happiness. That was one aspect of it, because grad school has this reputation for being a very challenging place and time in a scientist’s life. I wanted to be as happy as possible, even though I knew it was going to be extremely challenging.

I also thought that [the students] had two qualities (and this goes for the faculty as well) that can be hard to find in one place: they were exceptionally bright and exceptionally nice. That combination is not easy to find; at least I didn’t think it was easy to find. I really liked that. Especially the senior grad students in my program, I thought they were super brilliant and that I could learn a lot from them. I didn’t want to be in a program where I felt like I was the top recruit. I wanted to be in a place where I could learn as much as possible from everyone around me. So I didn’t attend the schools that I knew were actively trying to get me as their sort of shining star. That just didn’t really dovetail with my personality.

I had such an amazing time as a graduate student, just being part of the program. Looking back, relatively speaking, it’s a very progressive grad program. It’s very student-driven, and the faculty there really invest in [the students’] training. I felt like I was a young peer, and that really played a dramatic role in shaping me as a scientist — being taken seriously. It matters. There’s an intellectual independence that gets fostered in an environment like that. I wouldn’t hesitate to do it all over again, even with all the challenges of developing your thesis, doing the experiments, and all the hiccups. I thoroughly enjoyed my time there.

Q: Tell me about your research and training at Berkeley.

A: I [worked] with Shaowen Bao, who is now at the University of Arizona, doing work on how early life experience changes the brain. To be more specific, I studied critical period plasticity in the auditory system. This involves lots of neural recordings — in vivo electrophysiology in anesthetized animals. 

Cal’s Neuroscience Program is really strong in both experimental and computational neuroscience. Every lab I rotated in had strengths in both. I learned about information theory from Frédéric Theunissen and the latest decision-making theories from Joni Wallis. I took Bruno Olshausen’s computational neuroscience course at the Redwood Center for Theoretical Neuroscience, which is where I actually met my husband and collaborator, Badr Albanna [at the time, a graduate student in physics in the DeWeese lab]. In Bruno’s class, I worked on a project involving generative models using Kalman filters. I also learned about Bayesian models, efficient coding, sparse coding and dimensionality reduction. 

So I grew up, so to speak, in a scientific environment that values experimental and computational methods, and I ended up getting lots of experience in both along the way. That combination of both experiment and theory is something that has significantly influenced my science and the way that I view approaching scientific questions. I view that as an extremely valuable experience in terms of my scientific development.

With experimental neuroscience, especially when you’re dealing with neural recordings from hundreds of neurons simultaneously, you really need advanced computational methods to dissect and interpret those kinds of datasets because they’re so complex. They sort of feed off of each other, and I think that they’re a requirement, given the advancements in neural recording technologies and the fact that some people are actually already recording from thousands of neurons simultaneously. We’re going to need those computational tools. So I feel like I’m in a good position to make advancements because of the fact that I feel comfortable navigating those waters.

Q: What did you do after you graduated?

A: Like most graduate students, by the time I was wrapping up my PhD, I had developed this love-hate relationship with science. I saw all the pros and the cons and had to make a decision — do I apply for a postdoc or should I go in a different direction? But I still had ideas that I wanted to test. So I asked myself a very simple question: do I want to do this for another five years? The answer was yes, so I applied for postdoc positions. I didn’t think any further than five years — just do I want to spend the next five years of my life studying the brain? I’ve never had a grand plan to run my own lab or anything like that. Not at all.

For my postdoc, I became really interested in studying perception and behavior. It was an aspect that was completely missing from my graduate experience. To do this involves chronic recording in behaving animals, which is something that my postdoc adviser was interested in, but didn’t have working in his lab. So I reached out to my postbac adviser Andre Fenton, the one who was studying the hippocampus [laughs]; the one who propelled me into the direction of neuroscience research. And I asked if he would teach me the technique, because he had just moved to NYU when I was doing my postdoc at NYU.

I then translated the technique to the auditory cortex and started using tetrode microdrives to record from the brains of behaving animals, which is really one of the most exhilarating things I’ve ever done. While I was recording from sensory cortex, I noticed that only 40% of the neurons were highly responsive to sound, while the rest of neurons I recorded were very quiet. They didn’t appear to be responsive or modulated by the task at all. I took a closer look at the literature and I realized that many studies had reported the presence of these neurons, which were labeled non-responsive and often neglected from analysis. But given their prevalence, I began to wonder if these ‘dark matter cells’ (as I like to informally call them) were somehow relevant for behavior, and we just needed the right way to look at the data.

I developed a way to interpret their activity using a novel analysis. One of our major findings was that these quiet cells that we historically thought weren’t doing anything useful were, in fact, highly informative. We found out that they actually do participate in behavior, and they represent sounds in the environment as well as the decisions the animal made during a task. We published this manuscript in 2019 and I went on the job market that year. Now I’m an Assistant Professor in the Department of Otolaryngology at Pitt School of Medicine.

Q: What do you study in your lab?

A: My lab studies the neural basis of flexible behavior with a particular interest in how animals learn. For example, as we both have probably experienced, sounds encountered in daily life are really neutral. You may not notice the sound of a honking horn while stuck in traffic, but one heard while crossing the street might startle you. So how do we learn to interpret what we hear and act on it?

We use a wide range of techniques, including behavioral paradigms, neural recordings, optogenetic manipulation, and novel computational methods. We study rodents to take advantage of all the new genetic tools for probing neural circuits and their ability to quickly learn complex behavioral paradigms. That’s it in a nutshell.

Q: Your work has some clinical implications — tell me about that.

A: I’m really interested in learning and flexible behaviors, and I’m interested in studying that not just in the case of normal hearing, but also in the case of impaired hearing. One of the avenues of my lab involves studying cochlear implants. They are neural prosthetics that stimulate the auditory nerve and can restore hearing to the profoundly deaf ear. What’s really fascinating about those implants is that implant recipients have to learn to interpret these new signals that are coming from the ear. And they learn to use the implant over time. From my perspective, that’s fascinating, because it means that there’s a role for plasticity in the nervous system for shaping the learning trajectory of someone that has a cochlear implant. 

I’m really interested in what determines the outcomes for a cochlear implant recipient. For example, there’s a huge amount of variability in how quickly someone learns to use the implant. Some people can learn to use the implant in six months; some take longer. I’m really curious about why that variance exists and whether or not we can actually improve these learning trajectories for cochlear implant patients.

I’ve done some work that involves what I like to call ‘double bionic’ rats. These are deaf rats that are implanted with both cochlear neuroprosthetics and a high-channel recording array implanted over auditory cortex so that we can monitor neural signals as animals learn to use the implants. So we can combine behavioral performance with a neural readout to understand how they learn to use the implant to restore hearing. 

I started working on this model as a postdoc, and it’s something that I’m interested in working on in my own lab and possibly developing a closed-loop version of this, where you can actually reprogram the implant using information from the brain. There’s a big question [about] to what extent reprogramming can improve perception. Right now, if a cochlear implant recipient were to go to an audiologist, the audiologist would help tune that implant. We’re wondering whether or not we can use neural signals from the brain — EEG, for example, would be a really nice noninvasive way of collecting neural data — to help reprogram the implant for improved perception. So instead of the audiologist just using the recipient’s verbal report or their perceptual report, they could also use the neural signal as a tool for fine-tuning the stimulation protocols for the implant.

Q: What has it been like to start a faculty position during a pandemic? 

A: Honestly, the past year has felt like a bit of a sprint, just with the move to Pittsburgh and then setting up the lab. It’s been pretty stressful, but luckily one of the undergraduate researchers that I worked with at NYU followed me to Pitt to help me set up the lab this summer. I just got so lucky. It was wonderful to have someone with me side by side, someone I knew, a familiar face helping me set up. I now have three technicians and two undergraduate students, and we started collecting neural data a few months after opening the lab. I’ve been busy with neural recordings during behavior and expanding the lab as I’m actively recruiting graduate students and postdocs.

Being a PI [principal investigator] is a really interesting experience, because you have to wear many hats. There are moments where I feel like I’m the lab technician, postdoc, and manager all at once. But in terms of the science, the possibilities are endless. As far as I’m concerned, it’s a truly rare opportunity to study whatever questions fascinate me and make some interesting discoveries. What can be better than that? 

Despite all the stuff with the pandemic, I feel very fortunate that the labs have remained open here, and that we can do our science safely. I haven’t had any major hiccups. Sometimes when you’re a scientist you just keep moving forward and you don’t look back. That’s sort of been my approach so far [laughs].

By Rachel Henderson

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