Effect And Mechanism Of Glucocorticoid On Glutamatergic And GABAergic Neurons In The Amygdala

Objective: To investigate the effect and mechanism of glucocorticoid on subcellular compartments and interactions between excitatory and inhibitory neurons in the amygdala,which may be involved in the pathological processes of major depression and anxiety.Methods: Glucocorticoid influence was examined by chronically intraperitoneally injecting dexamethasone in the mice or by acutely washing dexamethasone to the brain slices including amygdala.The neurons were recorded by a Multi Clamp-700 B amplifier under the current-clamp for their intrinsic property and voltage-clamp for their synaptic activity.The functions of GABAergic neurons were studied including their active intrinsic properties and inhibitory outputs.The functions of glutamatergic neurons were studied including the active intrinsic properties and excitatory outputs.Action potentials at the amygdala neurons were induced by injecting the depolarization pulse.Use transgenic mice with genetically YFP-labeled glutamatergic neurons and GFP-labeled GABAergic neurons in the amygdala as the research object,dexamethasone was acutely(25?M)washed onto the brain slices or was chronically given(40mg/kg)by intraperitoneal injection once a day for one week.The neuronal spikes and synaptic transmission were recorded by whole-cell patching in the amygdala neurons of brain slices.The record indicator contained spontaneous inhibitory postsynaptic current and inter-spike-intervals on glutamatergic neurons and spontaneous excitatory postsynaptic current and inter-spike-intervals on GABAergic neurons,to investigate the effect and mechanism of glucocorticoid on subcellular compartments and interactions between excitatory and inhibitory neurons in the amygdala.Results: The chronic application of dexamethasone increases GABA release from inhibitory neurons and GABAergic receptor responses in excitatory neurons of the amygdala and the acute applicationof dexamethasone increases GABA release from inhibitory neurons of the amygdala.Dexamethasone increases the spike capability of inhibitory neurons in the amygdala.The chronic application of dexamethasone decreases glutamate release from excitatory neurons and increases glutamate receptor responses in the inhibitory neurons of the amygdala.The acute application of dexamethasone decreases glutamate release from excitatory neurons of the amygdala.Dexamethasone does not affect spike abilities of excitatory neurons in the amygdala.Glucocorticoid produced the differential effects of on inhibitory and excitatory neurons in the amygdala.The acute or chronic administration of dexamethasone all upregulates GABA release and GABAergic neuron spiking as well as downregulates glutamate release.The chronic administration of glucocorticoid also enhances the responsiveness of GABA receptors.Conclusion: Dexamethasone upregulates the action onto the glutamatergic neurons from GABAergic neurons by elevating presynaptic neuronal excitability,GABA release as well as postsynaptic GABAA receptor responses.Dexamethasone downregulates the action onto the GABAergic neurons from glutamatergic neurons by lowering glutamate release.The downregulation of glutamatergic neurons by glucocorticoid and the upregulation of GABAergic neurons impair their balance and these alternations imbalance neural networks in the amygdala toward inhibitory state,which leads to emotional disorders during stress and provide inspiration for the development of antidepressant drugs.