1. Academic Validation
  2. Ventral subiculum promotes wakefulness through several pathways in male mice

Ventral subiculum promotes wakefulness through several pathways in male mice

  • Neuropsychopharmacology. 2024 May 11. doi: 10.1038/s41386-024-01875-6.
Xue-Fen Zhang # 1 Yi-Dan Li # 1 Yue Li 1 Ying Li 1 Dan Xu 2 Lin-Lin Bi 3 4 Hai-Bo Xu 5
Affiliations

Affiliations

  • 1 Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.
  • 2 Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.
  • 3 Department of Pathology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China. linlinbi2016@whu.edu.cn.
  • 4 Center for Pathology and Molecular Diagnostics, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China. linlinbi2016@whu.edu.cn.
  • 5 Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China. xuhaibo@whu.edu.cn.
  • # Contributed equally.
Abstract

The ventral subiculum (vSUB), the major output structure of the hippocampal formation, regulates motivation, stress integration, and anxiety-like behaviors that rely on heightened arousal. However, the roles and underlying neural circuits of the vSUB in wakefulness are poorly known. Using in vivo fiber photometry and multichannel electrophysiological recordings in mice, we found that the vSUB glutamatergic neurons exhibited high activities during wakefulness. Moreover, activation of vSUB glutamatergic neurons caused an increase in wakefulness and anxiety-like behaviors and induced a rapid transition from sleep to wakefulness. In addition, optogenetic stimulation of vSUB glutamatergic terminals and retrograde-targeted chemogenetic activation of vSUB glutamatergic neurons revealed that vSUB promoted arousal by innervating the lateral hypothalamus (LH), nucleus accumbens (NAc) shell, and prefrontal cortex (PFC). Nevertheless, local microinjection of dopamine D1 or D2/D3 receptor antagonist blocked the wake-promoting effect induced by chemogenetic activation of vSUB pathways. Finally, chemogenetic inhibition of vSUB glutamatergic neurons decreased arousal. Altogether, our findings reveal a prominent contribution of vSUB glutamatergic neurons to the control of wakefulness through several pathways.

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