Just as my internship was about to wrap up, I finally got to running an optogenetics experiment! To give you a better idea of what we were doing, I’ve attached a diagram of the rodent brain for reference below.
For our project, we focused on the VTA (ventral tegmental area). This region of the brain is one of several sites that contain neurons that release dopamine, which is unarguably the primary neurotransmitter involved in goal-directed behavior (which can encompass drug-seeking, and more broadly drug abuse). The VTA innervates several regions in the brain, most notably the NAc (nucleus accumbens). Previous experiments have shown that the NAc is one of the primary pleasure centers of the brain, and rats will even forgo eating if given the opportunity to self-stimulate the NAc. In short, the act of stimulating the NAc can take precedence even over basic behaviors that guide survival. With that in mind, we wanted to observe if optogenetic stimulation of the VTA (which innervates the NAc) can bring about somewhat similar results. Other non-optogenetics experiments have shown VTA stimulation to be effective in doing so. Furthermore, it’s also been observed that only certain phenotypes of rats will actively self-administer VTA stimulation. For the most part, this experiment was basically a test run to see if we could obtain the predicted results, troubleshoot any problems that arose, and generally refine our experimental procedure for future projects.
Below are some pictures inside the optogenetics room during an experiment. Although it looks really ominous, the room is red because rats lack the photoreceptors in their eyes that absorb the wavelength corresponding to red light so, in a room illuminated by red light, they are effectively blind. I’m sure there are several reasons for doing this, for one, behavioral experiments are highly influenced by environmental context, and by blacking out every part of the room except for the actual behavioral apparatus the rats are put in, we can limit the effect of the context of the room on their behavior. Another potential reason could be that under regular lighting, the rats could see what is going on and get stressed out, making them harder to handle.
From the data we later collected and analyzed from the experiments, we were able to see significant differences in self-administration patterns between different phenotypes, showing us that despite all of the issues we ran into while getting this off the ground, we got pretty solid data to reward us for our efforts.
Looking back on my experiences working in the Flagel Lab this summer, I think I definitely gained more insight into the research process. It’s not the first time I’ve done research, but blogging and taking the time to reflect on what I was doing helped me to consolidate trends/ideas that came up throughout the summer. To begin, what you get out of research, especially as an undergrad, is a lot about taking initiative. This applies even more so if you are working independently of some preexisting research program since there are no real requirements to fulfill or deadlines to meet. That being said, the freedom of not being bound by program requirements can offer a lot of opportunities but at the same time, the near infinite paths you can take can also be very overwhelming. Without significant expertise in the field, it becomes more difficult to gauge which projects you can reasonably get involved in, and the amount of work you’d need to put in to run your own study semi-autonomously.
Going off that, if I were to give advice to another undergrad planning to pursue research, I would definitely suggest joining a lab under the structure of a program designed to facilitate the process of getting involved in research. The assignments and deadlines that these programs likely have will offer you opportunities to see real progress and also make sure your PI helps you meet those requirements. For example, wanting is much different from needing to do something by a certain time. Wants can be pushed off almost indefinitely but needs must be addressed appropriately. So the needs that come out of a structured program means that you will have to get stuff done and that your PI/lab would have to help you do so. Furthermore, the planning that goes into these types of programs saves you a lot of time that you would’ve spent creating your own schedule and determining adequate benchmarks of progress during your time at the lab. Finally, for the fiscally astute, these programs generally offer some sort of funding as well, usually in the form of a stipend.
However, as with all things, foresight is ultimately the key to success in the research setting. Whether or not you choose to conduct research through a program, advance planning is very necessary. Applications for research programs can be due up to half a year before decisions are released and having to deal with the possibility of not getting into the program makes consolidating summer plans a stressful and difficult experience. Conversely, just joining a lab can offer a lot of flexibility in terms of timing and summer planning but at the same time, if you’d like to get involved in experiments, things like room reservations, animal shipments, animal handling, and experimental parts have to be taken into account well in advance.
Regardless, I feel like I took a lot away from this experience—I can certainly see applications of the skills, experiences, and insight I’ve gained when it comes time for me to seek research opportunities in medical school.