GABAergic Neurons In Nucleus Accumbens Are Related To Resilience To Chronic Stress For Major Depression

Objective: Major depression,persistent low mood,is one of common psychiatric diseases.Its major etiology is thought to be chronic stressful environment,the sustained stress to the genetically vulnerable individuals leads to the dysfunctions of monoamine,brain-derived neurotrophic factor and hypothalamus-pituitary-adrenal axis,which evokes neuron atrophy in brain reward circuits at last.However,a large number of the individuals with experiencing chronic stress do not suffer from major depression,called as resilience.GABAergic neurons are vulnerable to chronic stress and their impairments is associated with major depression.It remains to be investigated the hypothesis whether these GABAergic neurons are vulnerable to chronic stress as well as involved in the resilience versus susceptibility to chronic stress for the suffering of major depression.The nucleus accumbens includes cell cluster only for GABAergic neurons in the limbic system and is thought to be one of family members in the brain reward circuit,its impairment is related to anhedonia.We hypothesize that the functional states of GABAergic neurons in the nucleus accumbens may be correlated to either resilience or susceptibility to chronic stress for major depression.Methods: Mice were treated by chronic unpredictable mild stress(CUMS)for 3 weeks.Depression-like behavior or resilience was confirmed by seeing whether their behaviors change significantly in sucrose preference,Y-maze and forced swimming tests.Mice from CUMS depression,CUMS resilience and controls were investigated in terms of GABAergic neuron functions in the nucleus accumbens by cellular electrophysiology.Results: The results of our experiment are as follows:1.Chronic unpredictable mild stress to the mice leads to either depression-like behaviors or resilience.2.GABAergic neuron outputs decrease in the nucleus accumbens from CUMS-induced depression-like mice,but not resilient mice;3.GABAergic neuron outputs decrease in the nucleus accumbens from CUMS-induced depression-like mice,but not resilient mice;4.GABAergic neuron excitability decreases in the nucleus accumbens from CUMS-induced depression-like mice,but not resilient mice;Excitatory synaptic transmission lowers on nucleus accumbens GABAergic neurons from depression-like mice.Thus,the functional states of GABAergic neurons in the nucleus accumbens are correlated to resilience versus vulnerability to chronic stress for major depression.Conclusions: The impairment of GABAergic neurons in the nucleus accumbens is associated with major depression.The invulnerability of GABAergic neurons to chronic stress may be one of cellular mechanisms for the resilience to chronic stress.