Dopaminergic modulation of basolateral amygdala for fear extinction
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flick-kflick-phd-bcs-2022-thesis.pdf
Description
Thesis PDF
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9.49 MB
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Adobe PDF
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38cdb728429adbf6708f07100834f59b
Author(s)
Flick, Katelyn
Advisor(s)
Tonegawa, Susumu
Date Issued
May 2022
Publisher
Massachusetts Institute of Technology
Abstract
The extinction of conditioned fear responses is crucial for adaptive behavior, and its impairment is a hallmark of anxiety disorders such as post-traumatic stress disorder. During fear extinction learning, a new memory is formed in basolateral amygdala (BLA) reward neurons, which inhibits the BLA fear memory. However, the neurological nature of the teaching signal that instructs the formation of fear extinction memory in BLA reward neurons is unknown. Recently work has identified a population of VTA dopamine neurons that signal shock omission during extinction, but a downstream target for that activity hasn’t been identified. In this thesis, I demonstrate the role of dopamine signaling in driving fear extinction in distinct BLA neuronal populations. We identify sources of dopamine and modes of dopaminergic action in the BLA, by showing that BLA fear and reward neuronal populations receive topographically divergent inputs from VTA dopamine (DA) neurons and differentially express dopamine receptors. Optogenetic activation of the VTA DA projections to BLA reward and fear neurons accelerated or impaired fear extinction, respectively. We found that dopamine D1 receptors (DrD1) expression in BLA reward cells is necessary for fear extinction. Furthermore, overexpression or optogenetic activation of DrD1 in BLA reward neurons accelerates fear extinction. Lastly, we record dopamine activity in the BLA and find that DA activity is time locked to freezing cessation in BLA reward cells and determine that this activity is correlated to the change in behavior observed during extinction. Together this thesis demonstrates that dopamine activity bidirectionally drives fear extinction by distinct patterns of activity at BLA fear and extinction neurons.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
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