Glucocorticoid Induces Incoordination between Glutamatergic and GABAergic Neurons in the Amygdala.

Guang-Yan Wang,Jin-Hui Wang,Zhao-Ming Zhu,Shan Cui,Anna-Leena Sirén

doi:10.1371/journal.pone.0166535

Abstract

BackgroundStressful life leads to mood disorders. Chronic mild stress is presumably major etiology for depression, and acute severe stress leads to anxiety. These stressful situations may impair hypothalamus-pituitary-adrenal axis and in turn induce synapse dysfunction. However, it remains elusive how the stress hormones mess up subcellular compartments and interactions between excitatory and inhibitory neurons, which we have investigated in mouse amygdala, a structure related to emotional states.Methods and ResultsDexamethasone was chronically given by intraperitoneal injection once a day for one week or was acutely washed into the brain slices. The neuronal spikes and synaptic transmission were recorded by whole-cell patching in amygdala neurons of brain slices. The chronic or acute administration of dexamethasone downregulates glutamate release as well as upregulates GABA release and GABAergic neuron spiking. The chronic administration of dexamethasone also enhances the responsiveness of GABA receptors.ConclusionThe upregulation of GABAergic neurons and the downregulation of glutamatergic neurons by glucocorticoid impair their balance in the amygdala, which leads to emotional disorders during stress.

Highlights

Major depression and anxiety are common psychiatric disorders, in which the dysfunctions of the neurons and synapses in the limbic system, such as amygdala, nucleus accumbens and PLOS ONE | DOI:10.1371/journal.pone.0166535 November 18, 2016Glucocorticoid Impairs Neuronal Interaction prefrontal cortex, are presumably involved [1,2,3,4,5,6,7,8,9,10,11,12,13,14]
The upregulation of GABAergic neurons and the downregulation of glutamatergic neurons by glucocorticoid impair their balance in the amygdala, which leads to emotional disorders during stress
Dexamethasone upregulates GABA release and GABAA receptor responsiveness in the amygdala The effect of dexamethasone, a synthetic glucocorticoid, on the action of the inhibitory neurons to the excitatory neurons was studied by recording spontaneous inhibitory postsynaptic currents (sIPSC) on glutamatergic neurons in the mouse amygdala, in which the mice were treated by the intraperitoneal injections of dexamethasone (DEX) once a day (40 mg/kg) for a week

Summary

Introduction

Major depression and anxiety are common psychiatric disorders, in which the dysfunctions of the neurons and synapses in the limbic system, such as amygdala, nucleus accumbens and PLOS ONE | DOI:10.1371/journal.pone.0166535 November 18, 2016Glucocorticoid Impairs Neuronal Interaction prefrontal cortex, are presumably involved [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. In terms of etiology for these emotional disorders, the physical and psychological stresses to the genetically susceptible individuals impair the functions of hypothalamus-pituitary-adrenal axis [15,16,17,18,19], and induce the neuron atrophy of the limbic system. Chronic mild stress is presumably major etiology for depression, and acute severe stress leads to anxiety. These stressful situations may impair hypothalamus-pituitary-adrenal axis and in turn induce synapse dysfunction. It remains elusive how the stress hormones mess up subcellular compartments and interactions between excitatory and inhibitory neurons, which we have investigated in mouse amygdala, a structure related to emotional states

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