Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons

The nucleus of Darkschewitsch (ND), mainly composed of GABAergic neurons, is widely recognized as a component of the eye-movement controlling system. However, the functional contribution of ND GABAergic neurons (ND_GABA) in animal behavior is largely unknown. Here, we show that ND_GABA neurons were selectively activated by different types of fear stimuli, such as predator odor and foot shock. Optogenetic and chemogenetic manipulations revealed that ND_GABA neurons mediate freezing behavior. Moreover, using circuit-based optogenetic and neuroanatomical tracing methods, we identified an excitatory pathway from the lateral periaqueductal gray (lPAG) to the ND that induces freezing by exciting ND inhibitory outputs to the motor-related gigantocellular reticular nucleus, ventral part (GiV). Together, these findings indicate the ND_GABA population as a novel hub for controlling defensive response by relaying fearful information from the lPAG to GiV, a mechanism critical for understanding how the freezing behavior is encoded in the mammalian brain.