Stress-induced plasticity of GABAergic inhibition

GABAergic neurotransmission is highly plastic, undergoing dynamic alterations in response to changes in the environment, such as following both acute and chronic stress. Stress-induced plasticity of GABAergic inhibition is thought to contribute to changes in neuronal excitability associated with stress, which is particularly relevant for stress-related disorders and seizure susceptibility. Here we review the literature demonstrating several mechanisms altering GABAergic inhibition associated with stress, including brain region-specific alterations in GABA _A receptor (GABA _AR) subunit expression, changes in chloride homeostasis, and plasticity at GABAergic synapses. Alterations in the expression of specific GABA _AR subunits have been documented in multiple brain regions associated with acute or chronic stress. In addition, recent work demonstrates stress-induced alterations in GABAergic inhibition resulting from plasticity in intracellular chloride levels. Acute and chronic stress-induced dephosphorylation and downregulation of the K ⁺/Cl ⁻ co-transporter, KCC2, has been implicated in compromising GABAergic control of corticotropin-releasing hormone (CRH) neurons necessary for mounting the physiological response to stress. Acute stress also unmasks the capacity for both long-term potentiation and long-term depression, in distinct temporal windows, at GABAergic synapses on parvocellular neuroendocrine cells (PNCs) in the paraventricular nucleus (PVN) of the hypothalamus. This review highlights the complexity in the plasticity of GABAergic neurotransmission associated with stress and the relationship to neuronal excitability, including alterations in GABA _AR expression, synaptic plasticity at GABAergic synapses, and changes in chloride homeostasis.