Chronic Stress Remodels Synapses in an Amygdala Circuit–Specific Manner |
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Authors: | Jun-Yu Zhang Tao-Hui Liu Ye He Han-Qing Pan Wen-Hua Zhang Xiao-Ping Yin Xiao-Li Tian Bao-Ming Li Xiao-Dong Wang Andrew Holmes Ti-Fei Yuan Bing-Xing Pan |
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Institution: | 1. Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, China;2. Department of Neurology, the 2nd Affiliated Hospital, Nanchang University, Nanchang, China;3. Human Aging Research Institute, School of Life Science, Nanchang University, Nanchang, China;4. Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China and Zhejiang Provincial Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China;5. Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China;6. Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland |
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Abstract: | BackgroundChronic stress exposure increases the risk of developing various neuropsychiatric illnesses. The behavioral sequelae of stress correlate with dendritic hypertrophy and glutamate-related synaptic remodeling at basolateral amygdala projection neurons (BLA PNs). Yet, though BLA PNs are functionally heterogeneous with diverse corticolimbic targets, it remains unclear whether stress differentially impacts specific output circuits.MethodsConfocal imaging was used to reconstruct the morphology of mouse BLA PNs with the aid of retrograde tracing and biocytin staining. The synaptic activity in these neurons was measured with in vitro electrophysiology, and anxiety-like behavior of the mice was assessed with the elevated plus maze and open field test.ResultsChronic restraint stress (CRS) produced dendritic hypertrophy across mouse BLA PNs, regardless of whether they did (BLA→dorsomedial prefrontal cortex dmPFC]) or did not (BLA?dmPFC) target dmPFC. However, CRS increased the size of dendritic spine heads and the number of mature, mushroom-shaped spines only in BLA?dmPFC PNs, sparing neighboring BLA→dmPFC PNs. Moreover, the excitatory glutamatergic transmission was also selectively increased in BLA?dmPFC PNs, and this effect correlated with CRS-induced increases in anxiety-like behavior. Segregating BLA?dmPFC PNs based on their targeting of ventral hippocampus (BLA→ventral hippocampus) or nucleus accumbens (BLA→nucleus accumbens) revealed that CRS increased spine density and glutamatergic signaling in BLA→ventral hippocampus PNs in a manner that correlated with anxiety-like behavior.ConclusionsChronic stress caused BLA PN neuronal remodeling with a previously unrecognized degree of circuit specificity, offering new insight into the pathophysiological basis of depression, anxiety disorders, and other stress-related conditions. |
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Keywords: | Amygdala Anxiety Prefrontal cortex Projection neuron Spine Stress |
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