Nucleus Accumbens Corticotropin-Releasing Hormone Neurons Projecting to the Bed Nucleus of the Stria Terminalis Promote Wakefulness and Positive Affective State
Gaojie Pan1 · Bing Zhao1 · Mutian Zhang2 · Yanan Guo3 · Yuhua Yan1 · Dan Dai1 · Xiaoxi Zhang1,4 · Hui Yang1,5,6 · Jinfei Ni1 · Zhili Huang2 · Xia Li3 · Shumin Duan1,71 Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China
2 Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, and Joint International Research Laboratory of Sleep, Fudan University, Shanghai 200032, China
3 Institute of Special Environmental Medicine, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226000, China
4 Neurovascular Center, Changhai Hospital, Naval Medical University, Shanghai 200433, China
5 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China
6 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China
7 NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310030, China
Abstract
The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying the relationship between arousal and emotion regulation in NAc remain unclear. Here, we investigated the roles of a specific subset of inhibitory corticotropin-releasing hormone neurons in the NAc (NAcCRH) in regulating arousal and emotional behaviors in mice. We found an increased activity of NAcCRH neurons during wakefulness and rewarding stimulation. Activation of NAcCRH neurons converts NREM or REM sleep to wakefulness, while inhibition of these neurons attenuates wakefulness. Remarkably, activation of NAcCRH neurons induces a place preference response (PPR) and decreased basal anxiety level, whereas their inactivation induces a place aversion response and anxious state. NAcCRH neurons are identified as the major NAc projection neurons to the bed nucleus of the stria terminalis (BNST). Furthermore, activation of the NAcCRH-BNST pathway similarly induced wakefulness and positive emotional behaviors. Taken together, we identified a basal forebrain CRH pathway that promotes the arousal associated with positive affective states.
Keywords
Corticotropin-releasing hormone; Wakefulness; Anxiolysis; Nucleus accumbens; Bed nucleus of the stria terminalis
