首页|Basal Forebrain Cholinergic Innervation Induces Depression-Like Behaviors Through Ventral Subiculum Hyperactivation

Basal Forebrain Cholinergic Innervation Induces Depression-Like Behaviors Through Ventral Subiculum Hyperactivation

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Malfunction of the ventral subiculum(vSub),the main subregion controlling the output connections from the hippocampus,is associated with major depressive disorder(MDD).Although the vSub receives cholinergic innerva-tion from the medial septum and diagonal band of Broca(MSDB),whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive.Here,we found that chronic unpredictable mild stress(CUMS)induced depres-sion-like behaviors with hyperactivation of vSub neurons,measured by c-fos staining and whole-cell patch-clamp recording.By retrograde and anterograde tracing,we con-firmed the dense MSDB cholinergic innervation of the vSub.In addition,transient restraint stress in CUMS increased the level of ACh in the vSub.Furthermore,chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors;and local infusion of atropine,a muscarinic receptor antagonist,into the vSub attenuated the depression-like behaviors induced by chemo-genetic stimulation of this pathway and CUMS.Together,these findings suggest that activating the MSDB-vSub cho-linergic pathway induces hyperactivation of vSub pyrami-dal neurons and depression-like behaviors,revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.

DepressionMedial septumSubiculumAcetylcholineCircuit

Nana Yu、Huina Song、Guangpin Chu、Xu Zhan、Bo Liu、Yangling Mu、Jian-Zhi Wang、Yisheng Lu

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Department of Physiology,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

Department of Pathophysiology,Key Laboratory of Ministry of Education for Neurological Disorders,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

Department of Physiology and Pathophysiology,Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province,School of Basic Medicine,Xinxiang Medical University,Xinxiang 453003,China

Department of Neurobiology,School of Basic Medicine,Huazhong University of Science and Technology,Wuhan 430030,China

Department of Otorhinolaryngology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China

Institute of Brain Research,Collaborative Innovation Center for Brain Science,Huazhong University of Science and Technology,Wuhan 430030,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China

820715083177119031730035

2023

10.1007/s12264-022-00962-2

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(4)
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