Cannabinoid modulation of central amygdala population dynamics during threat investigation

Cannabinoids precipitate anxiety and panic reactions in humans and can increase threat-related defensive responses in rodents in a dose- and context-dependent manner. Despite these well-established findings, how cannabinoids affect in vivo neural dynamics associated with threat-related behavior has not been examined. Here, we show that cannabinoids dose-dependently augment threat-induced defensive responses and the activity of central amygdala (CeA) somatostatin neurons (SOM) in mice, which are required for cannabinoid augmentation of threat avoidance, but not freezing. Moreover, enhanced antagonistic behavior-linked sub-ensemble generation, threat-related location and behavior representation, and multidimensional representation, were also observed after cannabinoid treatment. While cannabinoid receptor activation ex vivo suppressed excitatory inputs onto SOM neurons, our data suggest preferential suppression of local GABA release subserves cannabinoid activation of CeA SOM neurons. These data provide insight into how cannabinoid-mediated presynaptic suppression transforms postsynaptic population dynamics to reveal cellular mechanisms by which cannabinoids could affect threat-induced defensive responses.