Date: Monday, May 2nd at 1pm

Location: Simons Center for the Social Brain Conference Room 46-6011

Speaker: Kaytee Flick

Advisor: Susumu Tonegawa, PhD

Title: Dopaminergic modulation of BLA for fear extinction

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 subpopulation of basolateral amygdala (BLA) neurons, termed BLA extinction 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 extinction neurons is unknown. Recent work has identified a population of VTA dopamine neurons that signal shock omission during extinction. We hypothesize that the BLA extinction neurons are the downstream target of this activity. The omission of expected footshock increases VTA dopamine activity at  BLA extinction neurons to initiate fear extinction. In this thesis, we demonstrate that dopamine signaling drives fear extinction in distinct BLA neuronal populations. First, we show that BLA fear and extinction neuronal populations receive topographically divergent inputs from VTA dopamine neurons and differentially express dopamine receptors. Second, we use cell-type specific viral approaches to demonstrate that dopamine D1 receptor (DrD1) activity in BLA extinction cells is necessary for fear extinction. Third, to determine the natural dynamics of dopamine activity during fear extinction, we use fiber photometry to record dopamine activity in the BLA to reveal that DA activity is time-locked to freezing cessation in BLA reward cells, but not BLA fear neurons. Furthermore, the activity in BLA reward neurons correlates with extinction learning. Finally, optogenetic activation of the VTA DA projections to BLA reward and fear neurons accelerated or impaired fear extinction, respectively.  Together these results demonstrate that dopamine activity bidirectionally drives fear extinction by distinct patterns of activity at BLA fear and extinction neurons.