Mary Gates Endowment For Students

Sarah Thai

Mary Gates Research Scholar, Spring 2023

Research Project: Modulation of Anxiety-Like Behavior by Norepinephrine Signaling in the Basolateral Amygdala

Research Project Description:This study aims to elucidate stress-induced anxiety-like behaviors, with a specific focus on the noradrenergic signaling in the basolateral amygdala (BLA). Anxiety disorders represent a significant global health burden, affecting 30% of the population at some point in their lives. Unfortunately, the neurobiological mechanisms driving anxiety-like behaviors, particularly those induced by stress, remain incompletely understood. Past research indicates the limbic system, a group of interconnected brain regions, play a pivotal role in processing emotions and behaviors. Among these regions, the BLA is crucial for the expression of anxiety-like responses, receiving noradrenergic input from the locus coeruleus (LC). Although the LC’s involvement in promoting aversion and increasing anxiety-like behavior has been established, specific neuronal cell types and receptors responsible for these effects remain unidentified. Therefore in hopes of identifying these specific neuronal cell types and receptors, I will use CRISPR/SaCas9 gene editing technology to selectively knock down β adrenergic receptors in BLA neurons to prevent these receptors from responding to noradrenaline (NE) release in response to stress. Specifically, adrenergic receptors alpha-1 (Adra1a) and beta-2 (Adrb2) will be targeted in either glutamatergic or GABAergic BLA neurons to determine their distinct contributions to stress-induced anxiety-like behavior. I will then expose mice to a synthetic predator odor (trimethylthiazole) to elevate the tonic activity of LC-NE neurons and subsequently assess anxiety-like behavior using a series of well-established designs: Novelty-Suppressed Feeding (NSF), Open Field Test (OFT), and Elevated Zero Maze (EZM). To obtain unbiased behavioral data, a machine learning model based on Deep Lab Cut pose estimation and Simple Behavioral Analysis (SimBA) will be employed. The significance of this study lies in its potential to uncover precise cellular and receptor mechanisms that mediate anxiety and aversion induced by stress-induced tonic LC activation with the hopes of aiding in the development of more efficacious drugs for treating anxiety disorders.

What advice do you have for future Mary Gates Research applicants?

Just apply! My biggest advice is to always give it a try. The worst that could happen is that the opportunity doesn’t work out. In life and your academic career, you will face rejection (unfortunately, it’s inevitable). What matters most is how you pick yourself up, learn from the experience, and move forward, always giving your best. Work hard to achieve success. You’ve got this!

What have you learned throughout your research project? 

Throughout my research project, I’ve come to realize that experiments don’t always unfold as anticipated. It’s crucial to cultivate adaptability and creativity in refining the original experimental design. In my perspective, there’s no such thing as a failed experiment; it’s merely an opportunity to refine our approach in addressing the central question. We can either fine-tune the existing method or explore an entirely different one. Science is an ongoing process, and it’s through this journey that we encounter and surmount challenges, providing a source of pride in our accomplishments.