Description:

Jonathan P. Fadok, Ph.D., Assistant Professor, Tulane University, Department of Psychology

Abstract:

Survival requires the selection of appropriate behavior in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as posttraumatic stress and panic disorder. Threat-induced behaviors, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA). However, the source of neuronal excitation to the CeA that contributes to high-intensity defensive responses is unknown. In this presentation, I will discuss a newly discovered top-down pathway from the dorsal peduncular (DP) prefrontal cortex to the CeA that regulates defensive responses. We used a combination of neuroanatomical mapping, in vivo calcium imaging, functional manipulations, and slice electrophysiology to characterize the DP-to-CeA pathway. DP-to-CeA neurons are glutamatergic and specifically target the medial CeA, the main output nucleus of the amygdala controlling threat responses. Using a Pavlovian conditioning paradigm that elicits both freezing and flight, we find that CeA-projecting DP neurons are activated by high-intensity threats in a context-dependent manner. Chemogenetic and optogenetic manipulations revealed that the glutamatergic DP-to-CeA pathway is necessary and sufficient for both avoidance behavior and flight. Furthermore, we discovered that DP projections target distinct medial CeA neuronal populations projecting to midbrain flight centers. These results elucidate a non-canonical top-down pathway regulating defensive responses to threats.