Glucocorticoid Regulation of the GlutamatergicSynapse: Mechanisms of Stress-Dependent Neuroplasticity
N. V. Gulyaeva
Abstract
Glucocorticoids released from the adrenal cortex under the influence of stress factors are the most important messengers in the integrative regulation of adaptive plasticity of the brain, executed by the neurohumoral hypothalamic–pituitary–adrenal system. Excitatory synapses are considered as key elements in synaptic plasticity and behavioral adaptation. The review summarizes data on the mechanisms of glucocorticoid regulation of the glutamatergic synapse, primarily on the examples of the hippocampus and prefrontal cortex. Glucocorticoids, by triggering signal transduction through mineralocorticoid and glucocorticoid receptors located on synaptic membranes and in the cytosol of glutamatergic neurons, regulate synapse plasticity at the level of pre- and postsynaptic compartments. Glucocorticoids modulate synapse excitability through changes in vesicular transport and glutamate release, and mediate changes in the expression, composition, and properties of ionotropic NMDA and AMPA receptors, as well as other glutamate receptors. A detailed scheme of multiple regulatory mechanisms implemented in the glutamatergic synapse during the binding of glucocorticoids to specific receptors is presented.