A cingulate-hippocampal circuit mediates early depressive-like behavior in the mouse model of Alzheimer disease

Yanbing Chen; Huimin Peng; Kai Zhuang; Wenting Xie; Chenli Li; Meiqin Chen; Jin Xue; Xiaoting Huang; Tingting Zou; Hao Sun; Aiyu Lei; Ya Wang; Dan Can; Huifang Li; Tifei Yuan; Jie Zhang

doi:10.1016/j.isci.2024.109778

A cingulate-hippocampal circuit mediates early depressive-like behavior in the mouse model of Alzheimer disease

iScience. 2024 Apr 19;27(5):109778. doi: 10.1016/j.isci.2024.109778. eCollection 2024 May 17.

Authors

Yanbing Chen¹, Huimin Peng¹, Kai Zhuang¹, Wenting Xie¹, Chenli Li¹, Meiqin Chen², Jin Xue¹, Xiaoting Huang¹, Tingting Zou¹, Hao Sun¹, Aiyu Lei¹, Ya Wang¹, Dan Can¹, Huifang Li¹, Tifei Yuan³, Jie Zhang^{1

2

4

5}

Affiliations

¹ Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China.
² College of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
³ Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200000, P.R. China.
⁴ Department of Neurology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, P.R. China.
⁵ Institute of Neuroscience, Fujian Medical University; Fuzhou, P.R. China.

Abstract

Depressive symptoms usually precede the cognitive decline in Alzheimer disease (AD) and worsen the clinical outcome. However, the neural circuitry mediating early emotional dysfunction, especially depressive symptoms in AD, remains elusive. Anterior cingulate cortex (ACC) is closely related to depression and vulnerable in AD. By quantitative whole-brain mapping and electrophysiological recording, we found that the decreased axonal calcium activity in neurons of ACC and the glutamatergic projection from ACC to the ventral hippocampal CA1 (vCA1) is significantly impaired in 3-month-old 5×FAD mice, which exhibit depressive-like phenotype before cognition defects in early stage. The activation of ACC-vCA1 circuit by chemogenetic manipulation efficiently ameliorated the early depressive-like behaviors in 5×FAD mice. We further identified the upregulated neuregulin-1 (Nrg1) in ACC impaired the excitatory synaptic transmission from the ACC to vCA1 in AD. Our work reveals the role of ACC-vCA1 circuit in regulating AD associated depression symptom in a mouse model of AD.

Keywords: Behavioral neuroscience; Molecular biology; Neuroscience; Omics; Transcriptomics.