title: Alterations of motor cortical microcircuit in a depressive-like mouse model produced by light deprivation.
abstract: Depression is one of the most prevalent and life-threatening forms of mental illness. The heavy social burden imposed by this disorder calls for a better understanding of its pathogenesis. Light deficiency is an important factor potentially leading to depression. However, how the light deficiency affects neural microcircuit underlying depression remains largely unknown. This study investigated the properties of morphology, electrophysiology, and synaptology of layer V pyramidal cells (L5PCs) in the motor cortex of a mouse model with depressive behavioral phenotype that was produced by light deprivation (LD). The depressive behavioral phenotype was characterized by increased immobility and decreased locomotor activity in behavioral tests. LD decreased burst firing neurons and suppressed the intrinsic excitability of L5PCs, and also reduced the neuronal morphological complexity as evidenced by simplified basal and apical dendrites. Moreover, LD reduced the synaptic connecting probability of L5PCs. These alterations of the simplified morphology, the suppressed excitability, and the reduced connecting probability of L5PCs together could well explain the depression-like behaviors of the mouse model. However, it was surprising to find that the excitatory postsynaptic potentials (EPSPs) of single L5PC connections were significantly enhanced and the paired pulse ratio (EPSP2/EPSP1) was significantly increased. These synaptological results indicate that the absolute synaptic strength of single L5PC connections was enhanced and the transmitter release probability was increased although the connections between L5PCs became sparse. Therefore, a compensation mechanism accompanied the negative changes that were consistent with the depressive behavioral phenotype. Our findings from the motor cortex of depression-like behavior mice may underlie the neural microcircuit mechanism of depression, providing insights into the pathogenesis of depression at a level of single neurons and synaptic connections.
authors.affiliation: School of Ophthalmology & Optometry, The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P.R. China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, China. Electronic address: zhangyunfeng1983@163.com.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: School of Ophthalmology & Optometry, The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P.R. China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, China.
authors.forename: Qi-Qin
authors.initials: QQ
authors.lastname: Li
authors.affiliation: School of Ophthalmology & Optometry, The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P.R. China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.affiliation: School of Ophthalmology & Optometry, The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P.R. China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, China.
authors.forename: Cui-Min
authors.initials: CM
authors.lastname: Sun
authors.affiliation: School of Ophthalmology & Optometry, The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P.R. China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, China; Allen Institute for Brain Science, Seattle, WA 098109, United States. Electronic address: yun.wang@mail.eye.ac.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003712:Dendrites / Q000473:pathology / Q000502:physiology; D003866:Depressive Disorder / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D008027:Light; D008297:Male; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000502:physiology; D009044:Motor Cortex / Q000473:pathology / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D017966:Pyramidal Cells / Q000473:pathology / Q000502:physiology*; D012683:Sensory Deprivation; D013569:Synapses / Q000473:pathology / Q000502:physiology*
keywords: depression; layer V pyramidal cells; morphological complexity; paired pulse ratio; synaptic connecting probability; transmitter release probability