Corticotropin-Releasing Factor and Somatostatin Neurons in the Central Amygdala Mediate Dynamic Defensive Behaviors during Fear Extinction.

Traumatic experiences can result in heightened fear responses to trauma-associated stimuli. These symptoms can be difficult to extinguish, so identifying neuronal targets for facilitating fear extinction is critical. Many studies investigating fear learning in mice measure conditioned fear via freezing, but other defensive behaviors, such as flight, can also be present during conditioning. The central amygdala (CEA) mediates conditioned freezing and flight responses via corticotropin-releasing factor-positive (CRF+) and somatostatin-positive (SOM+) neuron populations. However, it is unknown how these populations regulate changes in freezing and flight responses as fear extinction is learned. Thus, we investigated the roles of CRF+ and SOM+ CEA neurons in modulating defensive behaviors during extinction. To elicit dynamic defensive responses in male and female mice, we used a modified pavlovian conditioned flight paradigm that paired an aversive footshock with a serial compound stimulus (SCS) consisting of tone followed by white noise (WN), resulting in freezing during the tone that rapidly transitioned into flight (escape jumping and darting) during WN. We used optogenetics in CRF-Cre and SOM-Cre mice to selectively excite and inhibit CRF+ and SOM+ CEA populations during WN presentation within extinction. Within early extinction, CRF+ inhibition reduced WN-evoked jumping and led to subsequent context-specific reduction in tone-evoked freezing. During extinction, SOM+ excitation replaced early WN-evoked flight with freezing, and both SOM+ excitation and inhibition reduced WN-evoked darting. Collectively, these data demonstrate modulation of jumping and darting behaviors within extinction via CRF+ and SOM+ CEA activity. These findings suggest mechanisms of attenuating multiple defensive behaviors during extinction.