A Parabrachial to Hypothalamic Pathway Mediates Defensive Behavior

Abstract

Defensive behaviors are critical for animal’s survival. The parabrachial nucleus (PBN) is critical in transmitting danger stimuli to trigger behavioral responses. Here, by viral tracing and electrophysiological recordings, we uncover that cholecystokinin (CCK) neurons in the lateral PB (LPBCCK neurons) are monosynaptic connected with the paraventricular nucleus (PVN) neurons. Selective photoactivation of LPBCCK neurons, their axon terminals within the PVN and glutamatergic neurons in the PVN, trigger defensive-like flight-to-nest behavior. Conversely, photoinhibition of LPBCCK neurons suppresses defensive responses. We show that LPBCCK neurons provide excitatory transmission to the PVN neurons and blocking glutamatergic transmission inhibits LPBCCK-PVN pathway activation-induced flight behaviors. Further, we demonstrate that chemogenetic inhibition of PVN neurons prevents photoactivation of LPBCCK-PVN pathway-driven flight responses. These data suggest that LPBCCK neurons recruit downstream PVN neurons to actively engage in flight responses. Our study identifies a novel circuit from LPBCCK to PVN and dissects its role in defensive behaviors.