Pathological Changes Of Gabaergic And Glutamatergic Neurons In Medial Prefrontal Cortex From CUMS-induced Depression Mice

Background: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.Methods:Using animal models of disease and genetically modified animals can help us to study the pathogenesis of human diseases. 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 versus controls.Results:In depression-like mice, the prelimbic cortical GABAergic neurons show incoordination among subcellular compartments, such as the decreased excitability and synaptic outputs as well as the increased reception from excitatory inputs. On the other hand, the glutamatergic neurons show the decreased inhibitory synaptic inputs, the increased postsynaptic responseness and no change in their excitability.Conclusions:Chronic unpredictable mild stress induces depression-like behaviors in the mice. The incoordination in prelimbic cortical GABAergic and glutamatergic neurons in depression-like mice dysregulates their target neurons, which may be the pathological basis for the depressive mood. The rebalance of compatibility among subcellular compartments would be an ideal strategy to treat neural disorders.