Neuroscience and Smell?

David Kedeme, COL ’25, Philadelphia, PA

Starting the summer as a rising junior, I was not fully sure if I was suitable to perform research but by the end of the summer, walking into the Ma Lab in Johnson Pavilion, in a section of the Neuroscience Department after many warm conversations and learning curves, I knew this was what I would aspire to do.

As I entered the lab, I did not know what to expect, but I was hopeful. With the compassionate and dedicated help of my family, mentors, and PI, I was able to learn and perform a range of techniques. These techniques included polymerase chain reaction or PCR for target genes such as somatostatin in a rhythmic breathing center brainstem area, slicing and mounting brains for differently targeted areas such as the olfactory bulb or a thalamic nucleus, and shadowing imaging of those slices from expression of GCaMP, a calcium sensor marking neuronal activity to seeing each neuron and their associated neurites. Ear tagging and cutting the tails of the mice was very scary and although I received a small bite once, I kept trying to pet them, which I did not have much luck with and kitchen gloves became handy. In tandem, behavioral analysis was also done of mice to have concomitant evidence with biological methods done as I learned how to analyze a paradigm called the three-chamber box test which is utilized for different social cognition processes such as social interaction and preference and novel interaction and preference. These mice had different perturbations, done to them via genetical manipulation, drug-induced manipulation, and surgery, done by lab members, in different neural olfactory regions which had relationships with other areas such as the prefrontal cortex. Whether the outcome was one that we wanted or not the one we wanted due to personal error or experimental error, I always felt comfortable, allowing for bonds to grow, and for learning to be smoother.

When you think of smell or olfaction, you think of the pleasurable sense of maybe flowers or perfume, tasty food, but also smells that are not as pleasurable such as gasoline, yet some do find engaging. But olfactory dysfunction is also, oftentimes, one of the first symptoms that comprise a multitude of diseases, including neurodegenerative, such as Parkinson’s disease, and neuropsychiatric, such as depression. Smell is thought to play a role in anxiety-like behavior, have connections with memory formation, and more.

Smell has many short- and long-range projections that signal throughout the complicated structure that is the brain. Where the neurons responsible for picking up different odors lie are located in an epithelium that is one of the spots of rapid regeneration yet inflamed by different conditions such as COVID-19, also having potential pathological implications. Breathing seems to entrain different areas of the brain during freezing behavior, the brain has structural differences concerning olfactory regions when it comes to schizophrenia, and nasal pathways have connections with areas such as the lateral habenula-ventral tegmental area system which might be a site for the mechanism of action of intranasal ketamine to take place, an emerging but cautionary prophylaxis for treatment-resistant depression, a type of depression in which an individual has not responded to two antidepressants given sufficient time. Smell is tied to a theory of experimental mice getting treated with methimazole, a drug that reversibly kills the nasal epithelium causes less socialization and that cause and effect is reversed back to a seemingly control state. These were some of the indicators of smell having more roles than the sense seemingly portrays.

As an aspiring physician-scientist, I would like to continue this journey of research in the Ma Lab for the upcoming years past university as well as there is an abundance of interest, peculiarity, and novelty when it comes to the field of neuroscience. What started off with the smell of what was an exciting, nervous summer and iced tea ended up being a summer that I will remember, including many smells.

This is part of a series of posts by recipients of the 2023 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here

By Career Services
Career Services