Valence encoding and memory in the amygdala
Author(s)Zhang, Xiangyu,Ph.D.Massachusetts Institute of Technology.
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences.
MetadataShow full item record
Assignment of valence, positive or negative, to external stimuli is essential to the formation of emotional responses. Information pertaining to an animal's emotional state serve as critical components of memories. However, the neural circuits which govern the valence representations, and which modulate the balance of their dynamic interactions are barely known. This thesis presents recent advances in understanding the valence encoding and emotional memories in amygdala circuits. We identified genetically-distinct neuronal populations in the central amygdala (CeA), examined their neural activity in response to appetitive or aversive stimuli, and characterized their functional contributions towards valence-specific behaviors. Using cell-type specific approaches, we dissected a basolateral amygdala (BLA)-to-CeA circuit that promotes and suppresses appetitive behaviors.This intra-amygdalar circuit motif reveals an organizing principle of genetic-specific representation of positive and negative valence in the mammalian brain. Next, we sought to examine the role of positive and negative neurons in control of fear memory. Using the engram-identification technique, we demonstrated that fear extinction memory is formed and stored in a genetically-defined population of BLA neurons that also drives reward behaviors and antagonizes BLA's fear neurons. The fear extinction engram cells and reward neurons are equivalent with regard to their neuronal representations within the BLA and their functions in driving appetitive functions and fear extinction behaviors. Accordingly, fear extinction is a newly formed reward memory. Lastly, we hypothesized that the absence of an expected aversive stimulus acts as a teaching signal for the amygdala-mediated fear extinction learning and memory.To this end, we demonstrated that dopamine receptor 1 (Drd1)-mediated dopaminergic transmission from the ventral tegmental area (VTA) dopamine neurons to BLA reward neurons facilitates fear extinction learning and memory, suggesting that dopamine may signal the aversive prediction error and recruit the reward circuitry to drive fear extinction behaviors. Collectively, our work sheds light on the cellular and circuit mechanisms underlying valence encoding and memories in the amygdala, and offers implications for developing therapeutic targets for emotional disorders, such as generalized anxiety disorder (GAD) and post-traumatic syndrome disorders (PTSD).
Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, May, 2020Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 167-184).
DepartmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology
Brain and Cognitive Sciences.