Major: Neuroscience Research Department: Neuroscience Graduation Date: August 2020
Abstract: The endocannabinoid system itself is a neuromodulatory system composed of endocannabinoids, their receptors, and the enzymatic constituents required for both synthesis and degradation. The two main endogenous lipophilic molecules responsible for the processes behind the endocannabinoid system, N-arachidonoylethanolamine (anandamide) (AEA) and 2-arachidonoylglycerol (2-AG), play a huge role in the regulatory systems of the body, and have been the main point of study due to its influence on many aspects of human health and disease progression. In Fragile X Syndrome, a genetic disorder causing mental disabilities due to the mutation of the fragile X mental retardation gene (FMR1), an apparent phenotype of the disorder is sensory hypersensitivity. In our lab’s previous studies, research has pointed to the imbalance of endocannabinoids as a cause of this circuit excitability. Through both excitation and inhibition, endocannabinoids control the probability of neurotransmitter release, resulting in the regulation of physical processes. In order to gain a better understanding of the complex systems at play, one would need to further identify which specific endocannabinoid has a more direct effect on the circuit hyperexcitability present in FXS and autism patients, as well as observe if the phenotype can be rescued using DO34- a DAGL inhibitor which would limit the release of 2-AG in the system.
What does research mean to you? As a Green Fellow, I was grateful for the opportunity to work with Dr. Kimberly Huber, a leading expert on synaptic plasticity. With my developing passion for mental disorders, it would be an understatement to say that I could not wait for my first full day in the lab. On this day, Dr. Huber explained to me that I would be working on the collection of UP states from layer V of the somatosensory cortex. Under the brilliant guidance of Dr. Gemma Molinaro, I was instructed on how to collect cortical somatosensory cortex slices, and it is here that I first realized I may have bit off more than I could chew. I attempted my way through the procedure, which ended up consuming the entire latter half of the afternoon. With all my initial first day excitement out the window, I begrudgingly began the walk towards Dr. Huber’s office, afraid of the potential scolding for being unable to complete the procedure within time. The response was anything but negative. She reminded me that procedures such as this take years of practice to perfect, and that research requires us to persevere through every obstacle along the way. Knowing that your work will potentially benefit the lives of thousands of people makes any trial or tribulation along the path worth the effort. It is here where I understood the value of research, and the traits it endows on those that choose to follow this pathway. Research simply translates to rigorous perseverance, combined with the necessity for creative thinking to tackle abstract problems. However, nothing is more important than just keeping your head up, and that is the biggest meaning behind it.
Tell us about your journey. My passion for research initially stemmed from the lure of neuroscience itself. The need for a deeper understanding brought me to Dr. Kilgard's synaptic plasticity lab, in which auditory remediation was assessed in regards to vagus nerve stimulation. It is here that I was first introduced to specific laboratory skills, such as micro construction and proper animal care. I then began a research experience with the NIH, focusing on plasticity in regards to visual restoration. However, the Green Fellowship program was always in the back of my mind, and the autonomy of the program itself brought me to the application screen.
How did the pandemic affect me? Sadly, the pandemic had cut short the on-hand experience of the program. Although our experiments were cut short, my lab did a fantastic job of keeping everyone involved in their experiments, and I was forever grateful for the opportunity to meet everyone in the Huber Lab.
Where am I now?
Advice for Future Green Fellows
Please make sure to take care of yourself throughout your journey. As neurotic undergraduates in pursuit of excellence in either medicine or research, we sometimes fail to allow ourselves even a moment to breathe. Over the course of this experience their will be times where you may feel overwhelmed, and it is of the utmost importance to remember that everyone you have met along your pathway-from your fellow Green Fellows to the wonderful Dr. Ravnik to your own research mentor- is here to see you succeed. Don't be afraid to reach out:)