Defensive behaviors are critical for animal’s survival. Both the paraventricular nucleus of the hypothalamus (PVN) and the parabrachial nucleus (PBN) have been shown to be involved in defensive behaviors. However, whether there are direct connections between them to mediate defensive behaviors remains unclear. Here, by retrograde and anterograde tracing, we uncover that cholecystokinin (CCK)-expressing neurons in the lateral PBN (LPBCCK) directly project to the PVN. By in vivo fiber photometry recording, we find that LPBCCK neurons actively respond to various threat stimuli. Selective photoactivation of LPBCCK neurons promotes aversion and defensive behaviors. Conversely, photoinhibition of LPBCCK neurons attenuates rat or looming stimuli-induced flight responses. Optogenetic activation of LPBCCK axon terminals within the PVN or PVN glutamatergic neurons promotes defensive behaviors. Whereas chemogenetic and pharmacological inhibition of local PVN neurons prevent LPBCCK-PVN pathway activation-driven flight responses. These data suggest that LPBCCK neurons recruit downstream PVN neurons to actively engage in flight responses. Our study identifies a previously unrecognized role for the LPBCCK-PVN pathway in controlling defensive behaviors.
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.
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