Incoordination among Subcellular Compartments Is Associated with Depression-Like Behavior Induced by Chronic Mild Stress.
Major depressive disorder is characterized as persistent low mood. A chronically stressful life in genetically susceptible individuals is presumably the major etiology that leads to dysfunctions of monoamine and hypothalamus-pituitary-adrenal axis. These pathogenic factors cause neuron atrophy in the limbic system for major depressive disorder. Cell-specific pathophysiology is unclear, so we investigated prelimbic cortical GABAergic neurons and their interaction with glutamatergic neurons in depression-like mice.



Mice were treated with chronic unpredictable mild stress for 3 weeks until they expressed depression-like behaviors confirmed by sucrose preference, Y-maze, and forced swimming tests. The structures and functions of GABAergic and glutamatergic units in prelimbic cortices were studied by cell imaging and electrophysiology in chronic unpredictable mild stress-induced depression mice vs controls.



In depression-like mice, prelimbic cortical GABAergic neurons show incoordination among the subcellular compartments, such as decreased excitability and synaptic outputs as well as increased reception from excitatory inputs. GABAergic synapses on glutamatergic cells demonstrate decreased presynaptic innervation and increased postsynaptic responsiveness.



Chronic unpredictable mild stress-induced incoordination in prelimbic cortical GABAergic and glutamatergic neurons dysregulates their target neurons, which may be the pathological basis for depressive mood. The rebalance of compatibility among subcellular compartments would be an ideal strategy to treat neural disorders.
College of Life Science, University of Science and Technology of China, Hefei Anhui, China (Ms Xu and Dr Wang); State Key Lab of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (Ms Xu, Ms Cui, and Dr Wang); University of Chinese Academy of Sciences, Beijing, China (Dr Wang).
Aiping
A
Xu
College of Life Science, University of Science and Technology of China, Hefei Anhui, China (Ms Xu and Dr Wang); State Key Lab of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (Ms Xu, Ms Cui, and Dr Wang); University of Chinese Academy of Sciences, Beijing, China (Dr Wang).
Shan
S
Cui
College of Life Science, University of Science and Technology of China, Hefei Anhui, China (Ms Xu and Dr Wang); State Key Lab of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (Ms Xu, Ms Cui, and Dr Wang); University of Chinese Academy of Sciences, Beijing, China (Dr Wang). jhw@sun5.ibp.ac.cn.
Jin-Hui
JH
Wang
D000818:Animals; D001522:Behavior, Animal; D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials; D005518:Food Preferences; D059330:GABAergic Neurons / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D018782:Maze Learning; D008822:Mice, Transgenic; D009043:Motor Activity; D009433:Neural Inhibition; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D013550:Swimming; D013997:Time Factors
D019422:Dietary Sucrose; D018698:Glutamic Acid
GABA; depression; glutamate; neuron; prefrontal cortex; stress