Thomas McGee ’22

Center for Neural Science at NYU, LeDoux Lab, New York, NY

This summer I interned in the LeDoux Lab at NYU. Throughout the summer I conducted behavioral experiments, data analysis, and all the neurosurgeries necessary for the optogenetics experiments that I ran. The LeDoux Lab studies the neural circuits that are responsible for threat-response acquisition and extinction in rodents. While I mainly performed optogenetics experiments in the lab (as part of postdoctoral research fellow Rodrigo Triana del Rio’s broader research project), we also use chemogenetic approaches, as well as various neuroimaging techniques and electrophysiology. Other postdocs at the lab study topics such as interindividual differences in threat-response acquisition and extinction, and how bacteria in the gut microbiome relate to subcortical brain circuits.

Preparing the shuttle boxes for an
optogenetic inhibition experiment.

My project involved deciphering the role of glutamatergic projections from the basolateral amygdala (BLA) to the nucleus accumbens (NAcc) in active avoidance. The BLA is a necessary module for selecting both passive and active defense behaviors. BLA-silenced rats exhibit increased startle potentiation, maladaptive 
freezing and reduced levels of active avoidance under exposure to an Timm. The NAcc is a structure in the ventral striatum that receives input from the BLA and is responsible for modulating reward and pleasure processing. While some researchers assert that the NAcc is responsible for emotional processing, it is presumably responsible for encoding some of the first-order non-conscious representations that are necessary precursors for the creation of meta-
representations that give rise to conscious feeling states. The NAcc is also 
crucial in the efferent pathway from the BLA, serving as an intermediary 
between the BLA and motor regions.

Recording baseline freezing and active avoidance levels in the Arduino boxes.

By inhibiting this projection using a viral opsin called archaerhodopsin, we saw that this inhibition caused active avoidance responses to develop more slowly and to a lesser degree compared to control groups. We hypothesized that glutamatergic projections to the NAcc mediate active avoidance behaviors by causing increases in levels of endogenous cannabinoids in the NAcc. Endocannabinoids modulate synaptic plasticity in the nucleus accumbens and are necessary for the acquisition of avoidance responses. Studies show that systemic manipulation of CB1R affects avoidance responses. Furthermore, in vitro optogenetic stimulation of glutamatergic BLA-NAcc projections increases levels of CB1R expression in NAcc MSN’s. It was exciting to see that these findings align with the behavioral responses observed under manipulation of CB1R via optogenetic inhibition of the BLA-NAcc pathway.

While I have enjoyed this research, I am interested in moving on to studying higher-order cognitive capacities in humans. Particularly, I am interested in studying the structural connective and representational underpinnings of higher-order cognitive capacities like language, emotion (conscious feeling states), and music cognition. This semester I am taking senior seminar courses in psychology and cognitive science, Bias and Discrimination and Topics Mind and Cognition, respectively. I am also taking a psychology course called Children’s Math Learning. I am looking forward to this course, because it is fascinating that sub-symbolic, connectionist systems such as the brain can conceptualize and manipulate discrete symbols like numbers. I am hugely grateful to the Class of 1994 for sponsoring this internship, the ’68 Center for Career Exploration, and everyone at the LeDoux Lab.