The basal forebrain to lateral habenula circuitry mediates social behavioral maladaptation

Jun Wang (), Qian Yang, Xue Liu, Jie Li, Ya-Lan Wen, Yuzheng Hu, Tian-Le Xu, Shumin Duan and Han Xu ()
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Jun Wang: Zhejiang University School of Medicine
Qian Yang: Zhejiang University School of Medicine
Xue Liu: Zhejiang University School of Medicine
Jie Li: Zhejiang University School of Medicine
Ya-Lan Wen: Zhejiang University School of Medicine
Yuzheng Hu: Zhejiang University
Tian-Le Xu: Shanghai Jiao Tong University School of Medicine
Shumin Duan: Zhejiang University School of Medicine
Han Xu: Zhejiang University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Elucidating the neural basis of fear allows for more effective treatments for maladaptive fear often observed in psychiatric disorders. Although the basal forebrain (BF) has an essential role in fear learning, its function in fear expression and the underlying neuronal and circuit substrates are much less understood. Here we report that BF glutamatergic neurons are robustly activated by social stimulus following social fear conditioning in male mice. And cell-type-specific inhibition of those excitatory neurons largely reduces social fear expression. At the circuit level, BF glutamatergic neurons make functional contacts with the lateral habenula (LHb) neurons and these connections are potentiated in conditioned mice. Moreover, optogenetic inhibition of BF-LHb glutamatergic pathway significantly reduces social fear responses. These data unravel an important function of the BF in fear expression via its glutamatergic projection onto the LHb, and suggest that selective targeting BF-LHb excitatory circuitry could alleviate maladaptive fear in relevant disorders.

Date: 2024
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DOI: 10.1038/s41467-024-48378-y

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