Cannabinoid Modulation of Central Amygdala Population Dynamics During Threat Investigation

Cannabinoids modulate innate avoidance, threat-reactivity, and stress adaptations via modulation amygdala-associated circuits; however, the mechanisms by which cannabinoids modulate amygdala representation of threat-related behavior are not known. We show that cannabinoid administration increases the activity of central amygdala (CeA) somatostatin neurons (SOM) and alters basal network dynamics in a manner supporting generation of antagonistic sub-ensembles within the SOM population. Moreover, diverging neuronal population trajectory dynamics and enhanced antagonistic sub-ensemble representation of threat-related behaviors, and enhanced threat-related location representation, were also observed. Lastly, cannabinoid administration increased the proportion of SOM neurons exhibiting multidimensional representation of threat-related behaviors and behavior-location conjunction. While cannabinoid receptor activation ex vivo suppressed excitatory inputs to 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 and reveal cellular mechanisms by which cannabinoids could affect threat-reactivity.