Excitatory and inhibitory neurons in the dorsal periaqueductal gray encode decisions to assess and escape natural threats

Abstract

Prey species are able to engage hardwired neural pathways to rapidly escape from an imminent predator attack. However, when predator threat is less probable they typically show a stereotypical sequence of approach toward the threat aimed at gathering more information, followed by escape to safety when the threat threshold is reached. The brainstem dorsal periaqueductal gray (dPAG) is required for the expression of escape behavior to predator threats and stimulation of dPAG elicits goal-directed flight. However, in vivo neural recordings in dPAG have identified separate populations of neurons that are tuned to either the approach or escape phase of the behavior suggesting that the structure may also be involved in threat assessment. The genetic identity and connectivity of these Assessment+ and Escape+ neurons have not been defined, although optogenetic activation of glutamatergic, but not GABAergic neurons elicits high-speed flight, suggesting that Escape+ neurons might be exclusively excitatory in nature. Moreover, it is not clear whether non-predator threats such as those elicited by conspecific or other animate threats are encoded by independent or overlapping neurons in dPAG. Here we report the activity pattern of ensembles of glutamatergic and GABAergic dPAG neurons during approach and escape from predator, social, and prey threats. Unexpectedly, we found that both glutamatergic and GABAergic neurons harbor Assessment+ and Escape+ neurons, suggesting that both cell-types are engaged in the approach-to-avoidance transition. Consistent with the functional involvement of both cell-types in approach-to-avoidance behavior, optogenetic activation of GABAergic cells elicited a reduction of risk assessment behavior towards the predator. Finally, we found that exposure to predator, social or prey threat recruited largely overlapping neurons in dPAG, demonstrating a convergence of threat processing in this structure. These findings point to a tightly coordinated role for dPAG excitatory and inhibitory neurons in the generalized control of innate threat assessment and avoidance behavior.