Puja Parekh

What is your area of research?

In the Liston lab, most of us are systems neuroscientists - we’re primarily interested in how neural circuit activity enables certain types of behaviors. Of course there is some redundancy, it’s not that each circuit uniquely controls any one behavior, but the more information we can get about parsing exactly what they do, is helpful to the field and of particular interest to the types of approaches that we employ.

What project are you most excited about right now?

My main project has centered on trying to understand the neural mechanisms underlying effort valuation. We make choices every day about how to spend our energy, and whether going for certain rewards is worth the effort it would take. Several psychiatric illnesses to some degree are characterized by deficits in reward processing, and sometimes in effort valuation. Depression, for instance: in some patients who have anhedonia, you suddenly can have a lack of interest, or not feel energetically driven to attain the same kinds of rewards. I would like to know where in the brain, and the prefrontal cortex and associated areas, do we have that information processing that allows for effort based decision making.

What is the coolest technique you’re using right now?

In-vivo two-photon calcium imaging is something that our lab uses regularly. It’s kind of a “bread and butter” technique of the lab I would say. It really is very powerful - it allows you to selectively target specific projection neurons that you might be interested in and monitor their activity over time. Imaging the medial prefrontal cortex can be challenging with conventional methods due to the fact that it’s deep within a fissure, so we use a technique that gives us access and preserves the structure and layers. Right-angle microprisms, implanted in the contralateral hemisphere, allow the light to be reflected through to image the medial aspect [of the prefrontal cortex]. It gives us the granularity of single cell imaging, and optical access to this really important region. Our imaging is time-locked to the animal’s behavior while it’s actively engaging in a learned task. That gives us a lot of data: we have behavioral variables, we have neural activity, and we can correlate the two and see which behavioral variables account for the most variance in neural activity.

Does your research have translational implications?

At this early stage in the project we don’t necessarily have a translational goal, but that’s always in the back of our minds. How the information that we learn can guide us towards something translational. With the Ketamine paper, it was very obvious: we wanted to understand the [anti-depressant] mechanism of Ketamine’s actions on the synaptic and circuit level. With the effort valuation, we can continue to test anti-depressants, both standard and non-conventional, but there’s a lot to learn still about the basic neurobiology of these circuits and how they’re driving various aspects of the behavior. Another very important thing we’re doing is also looking at how chronic stress perturbs both the behaviors and the circuit activity. In that sense, we want to see (again, like we did with the Ketamine paper) is there a dysfunction or dysregulation that stress produces that a certain antidepressant mechanism can counteract or normalize, and if so, in what ways specifically.

What do you love about NYC?

There’s lots of things to love about New York. There are the universal things that everybody thinks of, like the culture, food, architecture, history, and all that - which I value as well, but for me, I’m very much into understanding people's interactions with their environment and their city. New York offers endlessly fascinating observations of people and their relationship with the city, so that’s something that I think about a lot. Like most of us in academia, I’ve moved around a lot. Everywhere I’ve been, I think about how it’s shaped me, my beliefs, and my behaviors. With New York, I’m always reflecting on how NY is changing me as a person and what I’m learning about people. I think it’s a really fascinating city because the people are like one entity, and it’s us against the city sometimes. I think about that a lot and I really appreciate New York for its complexity and giving me all these instances to observe human nature.

It’s also cool to see the different local culture of the neighborhoods and boroughs and to compare them. When I’m in Manhattan I feel different than when I’m in Astoria. It almost feels like you are out of the city, or in a smaller city.

What is your favorite pizza topping?

I really like mushrooms, which I know aren’t everyone’s thing, but there’s this certain pizza (https://www.retropizzaastoria.com/) that I like that has three or four different kinds of mushrooms and truffle oil. That’s been my favorite so far because it’s unique. I’m a vegetarian, so I get protein and it feels slightly healthy, even if I know it’s not.

What new hobby or habit did you pick up during quarantine?

It was my first time teaching [Behavioral Neuroendocrinology] remotely, so I put a lot of effort into trying to adapt my in-person lectures to online. In terms of new skills, that helped me develop the ability to flexibly adapt my lectures to online. It was really interesting to check-in with my students, and see what worked for them in terms of teaching style. That’s something that I’ll definitely carry forward - even if I’m teaching in person in the future - understanding what’s most effective for them. We had a lot more dialogue: “What’s working? What’s not working?” It was stressful, but it was a way to grow in my lecturing style. It challenges you in a different way, but I think it’s still important regardless of the circumstances.

Do you feel like your experience with training mice has translated well into your experience training your cat?

I always try to draw parallels to the behavior that I observe in my cat and that I observe in my mice. They’re very different animals, one’s a predator and one’s prey, so they’re obviously going to react differently to what’s going on in the environment. But, it’s very clear that animals can be conditioned pretty easily by reward, and by food. My mice, as soon as they go into their head-fixing post they will start licking towards something. They’ve come to associate the context with the task even if I’m not running the task. Same with my cat: he hears a drawer open, and there was one time that there was a toy in the drawer that he wanted… It’s very hard to extinguish the associations after they’ve taken on some kind of meaning. I’m always interested to see what he is capable of learning and I’ve tried to push the limits there.

Have you taught your cat any tricks?

He’ll jump up for a treat and he’s gotten pretty good at grasping the treat in his paws. He learned that if he swats it, it will go on the floor and he has to scamper around for it. So he’ll grab it and he eats it out of his paw. I think out of laziness of not wanting to have to hunt the treat down, he learned a little bit of skill. I study effort valuation with the mice, so I’ll test his effort valuation sometimes, where I have this ball that I’ll put some chow into, it has little slits and he has to roll it around to get the pellets to fall out. At some point he just decides it’s not worth the effort of pushing it around and just gives up on it. So I’ve been tracking his willingness to work for reward. He’s becoming less and less willing as he ages I think.

What would people be surprised to learn about you?

My dad had a machine shop that was the family business. When I was younger I used to work in the machine shop. As a 14 year old, running machines is kind of strange, but it gave me this appreciation for mechanical devices. Something about being in [the Liston] lab that has been really unique to my training is that we build the behavioral setups we use, ourselves. We had a really talented technician with an engineering degree who was taking the lead, but in working with him and helping design them, I learned a lot about how to put things together. It goes back to my past where I really liked being around the shop, and trying to connect things, and make little machines and devices.

It’s practical and I think it’s becoming a trend in the field to customize your behavioral apparatus and imaging apparatus to exactly what you’re trying to do. So this ‘do it yourself’ culture is becoming prominent in certain kinds of systems labs. For me it’s been fun, challenging, stressful, but very interesting.

What is the best part about being a postdoc?

Independence. Most of us were in graduate training programs that are structured in a way that they are trying to give you well-rounded exposure to what it means to be an academic scientist. You have certain skills that you have to learn, and the program is checking up to make sure you’re learning those skills in a timely way. I remember there being a lot of assignments and evaluations and milestones, which was great for training at that stage. When I started my postdoc I was like wow no one expects me to be completing these “milestones” per se, on a regular basis, so you can be free to think about your questions and come up with challenging ways to approach answering your questions. In graduate school it felt like you were a little bit constrained by several factors. You kind of needed to be making progress at a certain rate, and it wasn’t always up to you what that rate was. So I would say the best part for me is freedom to explore what I want without as many demands on my time outside of doing research.

What advice would you give incoming postdocs? [audio link below!]

When I started in this new lab, there were techniques I had to get under my belt that took me a while. It was a steep learning curve and I remember feeling at one point like “maybe I just won’t get this, maybe I can’t do these experiments”. I thought I had maybe hit a limit because the progress I was making felt a lot slower than what I was used to in grad school. I remember several months of this “oh no, have I made a huge mistake, should I have just gone into a lab where from Day 1 I could step in there and be doing something I was good at”. But then I just thought “you know, everything I’m doing now is something I’ve never done before”. I think you have to give yourself a break sometimes. You have to just remember sometimes that you’re still learning, and you’re still a student, even when you feel like “I shouldn’t be a student anymore, I should be proficient and an expert”. I think we’re always going to have to reinvent ourselves in a way, staying in academia, so you have to cut yourself some slack and remember that you’re taking on something new. Know your limits, ask for help, and feel okay to feel like a trainee.