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
Affiliations
Yanbing Chen
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Huimin Peng
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Kai Zhuang
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Wenting Xie
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Chenli Li
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Meiqin Chen
College of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
Jin Xue
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Xiaoting Huang
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Tingting Zou
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Hao Sun
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Aiyu Lei
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Ya Wang
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Dan Can
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Huifang Li
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Tifei Yuan
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200000, P.R. China
Jie Zhang
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China; College of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China; Department of Neurology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, P.R. China; Institute of Neuroscience, Fujian Medical University; Fuzhou, P.R. China; Corresponding author
Summary: 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.
