Induction of flight via midbrain projections to the cuneiform nucleus.

The dorsal periaqueductal gray is a midbrain structure implicated in the control of defensive behaviors and the processing of painful stimuli. Electrical stimulation or optogenetic activation of excitatory neurons in dorsal periaqueductal gray results in freezing or flight behavior at low and high intensity, respectively. However, the output structures that mediate these defensive behaviors remain unconfirmed. Here we carried out a targeted classification of neuron types in dorsal periaqueductal gray using multiplex in situ sequencing and then applied cell-type and projection-specific optogenetic stimulation to identify projections from dorsal periaqueductal grey to the cuneiform nucleus that promoted goal-directed flight behavior. These data confirmed that descending outputs from dorsal periaqueductal gray serve as a trigger for directed escape behavior.

Prefrontal cortical control of a brainstem social behavior circuit.

The prefrontal cortex helps adjust an organism's behavior to its environment. In particular, numerous studies have implicated the prefrontal cortex in the control of social behavior, but the neural circuits that mediate these effects remain unknown. Here we investigated behavioral adaptation to social defeat in mice and uncovered a critical contribution of neural projections from the medial prefrontal cortex to the dorsal periaqueductal gray, a brainstem area vital for defensive responses. Social defeat caused a weakening of functional connectivity between these two areas, and selective inhibition of these projections mimicked the behavioral effects of social defeat. These findings define a specific neural projection by which the prefrontal cortex can control and adapt social behavior.