Induction of Conditional Fear Extinction

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DESCRIPTION (provided by applicant): Since Pavlov, conditional fear in mammals has been an important model of both associative learning and human anxiety. Briefly, animals rapidly learn to fear a neutral conditional stimulus (CS), such as a tone, when it is temporally paired with an aversive unconditional stimulus (US), typically a mild footshock. A subsequent exposure to the CS-alone elicits a robust conditional fear response (CR) in rodents, including freezing behavior. With repeated CS exposures the CR can strengthen (incubation) or weaken (extinction) depending on the temporal pattern of exposures. Extinction of fear is an active learning process resulting in the formation of an inhibitory memory that blocks fear expression. This proposal will focus on the cellular mechanisms underlying the induction of extinction memories. Aim 1 will attempt to define the minimum amount of CS exposure necessary to induce an extinction memory through a series of simple behavioral experiments. Aim 2 will investigate the potential role of amygdalar post-synaptic L-type voltage gated calcium channels (L-VGCC) in extinction memory induction, using systemic and local infusion of L-VGCC antagonists. Since extinction serves as the explicit model for behavior therapy of anxiety disorders, the findings may provide a foundation for improved psyhotherapies and adjunctive treatments.