Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons

Huiying Zhao; Jinrong Liu; Yujin Shao; Xiang Feng; Binhan Zhao; Li Sun; Yijun Liu; Linghui Zeng; Xiao-Ming Li; Hongbin Yang; Shumin Duan; Yan-Qin Yu

doi:10.1093/nsr/nwae082

Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons

Natl Sci Rev. 2024 Mar 5;11(4):nwae082. doi: 10.1093/nsr/nwae082. eCollection 2024 Apr.

Authors

Huiying Zhao^{1

2

3}, Jinrong Liu^{1

3}, Yujin Shao^{1

3}, Xiang Feng^{1

3}, Binhan Zhao¹, Li Sun^{1

3

4}, Yijun Liu^{1

3

4}, Linghui Zeng⁵, Xiao-Ming Li^{1

2

4}, Hongbin Yang^{1

3

4}, Shumin Duan^{1

3

4

5}, Yan-Qin Yu^{1

2

3

4

5}

Affiliations

¹ Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China.
² Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China.
³ Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou 311121, China.
⁴ NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 310058, China.
⁵ Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou 310015, China.

Abstract

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.

Keywords: GABAergic population; defensive behavior; freezing; neural circuitry; nucleus of Darkschewitsch.