Author Archives: Nithin Ragunathan

After a grueling, yet rewarding 8 weeks of lab work, BSURF 2019 has concluded.

My summer experience culminated Friday evening with the Duke Summer Undergraduate Research Showcase (pictured above), during which I presented my poster.

This summer has been a whirlwind, to say the least. Feeding mice, analyzing data, and learning about neuroscience all day, every day for 8 weeks was taxing, but extremely influential in my life and my career. Over the past few months, I feel that I accomplished a lot with my project in the Yin Lab, but more importantly, I feel that I’ve solidified a career interest in academic science— I’ve always seen it as a possibility, but thanks to my research, the faculty talks, and other BSURF programming, I know that this career path and this lifestyle are ones that I would enjoy.

I’d like to thank the Yin Lab and Francesco for hosting/mentoring me this summer, as well as the BSURF program for their support and funding this summer. This formative experience wouldn’t have been possible without the support of these people, and I’m grateful for them.

For the future, I remain hopeful. I plan to return to the Yin Lab and continue my work during the semester. I’ll be taking a full slate of courses and I’ll have to reduce my hours, but I’m looking forward to the next steps of my project and undergraduate experience.

This week, I’ve prepared an early draft of the abstract for my poster:

The anterior cingulate cortex (ACC) is a cortical brain region implicated in a variety of functions, including emotional self-regulation and the reward pathway. This project utilizes optogenetic stimulation techniques to both excite and inhibit the ACC in the mouse brain. Two opsins, channelrhodopsin and Guillardia theta anion channelrhodopsin 2 (GtACR2), were used to excite or inhibit the ACC respectively. Food deprived mice were trained to press a lever under different fixed ratio schedules. The mice were then given the same lever pressing task during intermittent periods of high frequency stimulation. Preliminary analysis of the lever press rate indicates a clear reduction in the amount of presses during stimulation periods when compared to nonstimulation periods in mice with the excitatory channelrhodopsin expressed, with no similar reduction in control mice. Given that mice are pressing less when the ACC is excited, there is reason to believe that, absent of motor impairment, the ACC is implicated in the effort-reward decision making process in the rodent brain.

Opioids are an impending crisis in this country and across the globe. The prescription of these heavy painkillers is highly controversial, with some medical professionals claiming that it’s too much and others claiming it’s too little— but we know one thing: substances like morphine and oxycodone are extremely powerful, but, more dangerously, extremely addictive. Knowing that these substances pose this threat, we ought to search for reliable alternatives that can improve people’s pain management without decimating their quality of life.

    As discussed in his chalk talk this week, Michael Lee’s lab is looking at pain response and reduction in the body through the use of a mouse model. Essentially, Michael’s job is to understand the pain threshold for mice through exposure to different stimuli, such as a filament poking their paws. He then observes if there is any notable behavioral change to determine if the mice are feeling pain. The project as a whole is exploring the use of a protein called STING (stimulator of interferon genes) that’s part of our innate immune response for its potential as a painkiller. Most painkillers attack the nervous system response for pain, but few do an adequate job of addressing the cycling neuroinflammation that accompanies injury, but STING, if expressed in greater amounts, could benefit people by offering a less addictive anti-inflammatory as a response to opiates or other commonly used pain killers.

    However, with STING, there are still concerns. Mainly, it needs to be target specific when expressed through therapeutic means. Pain is an essential signaling mechanism for the body in response to harm, and, though chronic pain is bad, pain does serve an important role in preserving our bodies. It’s certain that Michael’s research is both intriguing and applicable to everyday life, and I look forward to hearing more about what comes from his time in the lab.

This week, I had the opportunity to sit down with the principal investigator of my lab, Associate Professor Dr. Henry Yin of the Duke Department of Psychology and Neuroscience. I’d like to personally thank him for taking the time to talk to me about his experiences in science, research, and life in general, as well as for welcoming me into his lab. It’s through the generosity of Dr. Yin that I’m able to work in a lab and train as a young scientist, and I can’t express how grateful I am for the opportunity he’s given me this summer.

This interview, in particular, allowed me to pick the brain of an adult scientist— someone who knows what it takes to do well in the field and get results. As a nineteen-year-old, I consider myself extremely fortunate to have the opportunity to receive mentorship from Dr. Yin, and I hope that this as myself and this relationship continue to develop, I will improve as a scientist and better understand the ins and outs of academic research in neuroscience.

Q: What were your beginnings in science? Where did you study and where have you worked as you built your career?

A: Dr. Yin attended Washington University of St. Louis for his undergraduate studies. While working in a molecular lab during the summer prior to his junior year, he started reading neuroscience books, including those by Oliver Sacks. A lot of these books were about “big ideas” in neuroscience like language and human memory, which really sparked his interest in the field. After getting interested in neuroscience, he went to graduate school at UCLA expecting to work with human language and memory, but ended up studying rodents and the neural substrates of actions.

He considers himself lucky in that his early projects had moderate success, which further interested him in a career in science, while some of his peers had difficulty getting results and were thus somewhat alienated from research. He described this using an analogy to golf, saying that people who are naturally talented or have a great coach early on tend to continue with it while others who are less successful tend to give up more easily. After completing his graduate degree, he completed a postdoc at the NIH, working on cellular and molecular plasticity, long-term potentiation, long-term depression, and synaptic plasticity. He says he’s worked on the basal ganglia for his entire career and feels fortunate to have done so.

Q: What’s been your most meaningful accomplishment in science thus far?

A: Dr. Yin is proud of the work he’s done at Duke. His work has led to increased understanding of the basal ganglia and he believes that his results have been meaningful. To him, it’s about the results, not the career trajectory or title.

Q: If you could change one thing about how science is done, what would it be?

A: Dr. Yin expressed displeasure with what’s known as “careerism”. He believes that science should be about the passion for understanding nature and getting results, but believes that often people view it too much as a career. “It’s a cool job. You get to travel and there’s not as much pressure as a corporate job.” It’s for this reason that he thinks that a lot of researchers focus more on the prestige, status, and money rather than the results of their research and love for discovery.

Q: If you could go back in time and speak to yourself as an undergraduate around the age of 19 or 20, what’s the number one piece of advice you would give yourself?

A: Dr. Yin expressed the importance of seeking advice from people you really admire. He said that “Students will be willing to spend 200+ hours studying orgo or something to get an A vs a B+, but they don’t think to put in time like that to seeking advice from other people. There are many interesting people on campus.” He believes that a great deal of knowledge can be acquired from others and students should fully take advantage of it.

My parents have always given me advice and often I’d respond with an “OK, mom, got it,” disregard the advice, and move on with my day, but in the past year, I’ve encountered so many situations in which something they said turned out to be the best advice possible. I’ve realized that maybe these people who’ve lived for 30 years longer than me, gone to college, and earned a living for themselves might actually know something about how to be successful.

That’s the type of mentality I’ve decided to bring into the lab because I believe that the magic of Duke lies in the people we meet here. Dr. Yin and the others in my lab know what neuroscience research entails because they’ve done it for years, and I get to come into the lab as a sponge and soak up as much of their wisdom as possible. I’m grateful to be here and receiving advice from people I admire like Dr. Yin is something that I’m learning to make a priority. Dr. Yin demonstrated to me that becoming a successful scientist requires a can-do attitude, persistence, communication, and, most importantly, a willingness to learn. With these traits in mind, I will continue to work hard in the lab and talk to those around me in order to best capitalize on my time here in the Yin Lab.

The great American philosopher Alicia Keys once declared that “Big lights will inspire you” on a track with Jay-Z.

It’s this sentiment that I’ll be spending my summer trying to extrapolate to my mice. See, my project involves optogenetic stimulation of the brain. Optogenetics is a brain stimulation technique that relies on light. Basically, a surgeon puts some implants in a specific region of the mouse brain, we hook up the mice to some optic fibers, and then we use light on that brain region to stimulate it.

Optogenetics is a powerful technique because it allows us to pinpoint certain regions and see how behavior is altered by either activation or inhibition of those regions. In my project, we’re trying to see how activation and inhibition in the prefrontal cortex affects operant learning (learning to perform a task to obtain a reward). To test this, I’ve spent some time training mice to press a lever under different reward schedules. First, they learned that one press of a small lever leads to the release of one pellet of food. After 3 days of that schedule, I ramped it up to 5 lever presses for one pellet of food, and then finally to 10 lever presses for one pellet of food. The first day, they’ll take two hours and maybe press the lever 20 times or so, but within 2 days of training, they’ll press it 50 times in less than 10 minutes. It’s just like us humans— if we’re hungry and want food, we’ll figure out what it takes to get it.

After the first 9 days of training and eagerness to see the results of the experiment, I initialized the optogenetic stimulation for the first time on Saturday. The operant conditioning chambers in the lab are each equipped with motion sensors to track when the mice put their little heads in the feeding area and each box is connected to two computers that control the illumination and track how many times each mouse presses the lever to obtain a food pellet. Right now, I’m focused on collecting data and processing it so that I can start to make graphs for the analysis this upcoming week.

If I’m able to observe a significant change in the lever pressing behavior in response to illumination, we could develop a more detailed model of the operant learning pathway that’s being studied in other projects in the lab as well. The results from Saturday and Sunday will be my first optogenetic results of the summer, and I’m looking forward to seeing if the data I gathered can implicate the implanted brain region into the operant learning pathway.

Me in the lab

Making the long walk from French Family Science Center to Genome Sciences Research Building II into the Yin Lab for the first day of BSURF, I felt nervous about my first day in the lab. I didn’t know what to expect. I’d spent a few weeks in chemistry lab during one summer in high school, but I knew this experience would be different— I’d never worked with live animals before, a component integral to the research being done in the Yin Lab.

During my first week in the lab, all of my reservations about being in the lab over the summer were put at ease. The postdoc with whom I’m working, Francesco, helped me every step of the way, showing me how to handle, feed, weigh, and train my 8 mice. My project relates to the mechanisms of operant learning in the mammalian brain. To analyze this pathway, we’re using a technique called optogenetic (light-based) stimulation in the mice brains. Essentially, when we illuminate the implanted region of the brain, it’ll either be stimulated or inhibited. Then we’ll try to see if that effect hurts each mouse’s ability to learn how to press a lever and receive a pellet reward.

I’m extremely excited about this project and my summer in the lab. I’ve already met tons of insightful and experienced individuals in both my lab and in the BSURF program. I’m coming into this experience with an open mind. I have two goals this summer: learn lab skills and meet people to learn about them and their science. The BSURF program is well-structured for both of these goals. I’m loving my time this summer, and I’m excited for what’s to come.