Altered expression of delta GABA(A) receptors in health and disease

gamma-Aminobutyric acid type A receptors that contain the delta subunit (delta GABA(A) receptors) are expressed in multiple types of neurons throughout the central nervous system, where they generate a tonic conductance that shapes neuronal excitability and synaptic plasticity. These receptors regulate a variety of important behavioral functions, including memory, nociception and anxiety, and may also modulate neurogenesis. Given their functional significance, delta GABA(A) receptors are considered to be novel therapeutic targets for the treatment of memory dysfunction, pain, insomnia and mood disorders. These receptors are highly responsive to sedative-hypnotic drugs, general anesthetics and neuroactive steroids. A further remarkable feature of delta GABA(A) receptors is that their expression levels are highly dynamic and fluctuate substantially during development and in response to physiological changes including stress and the reproductive cycle. Furthermore, the expression of these receptors varies in pathological conditions such as alcoholism, fragile X syndrome, epilepsy, depression, schizophrenia, mood disorders and traumatic brain injury. Such fluctuations in receptor expression have significant consequences for behavior and may alter responsiveness to therapeutic drugs. This review considers the alterations in the expression of delta GABA(A) receptors associated with various states of health and disease and the implications of these changes. This article is part of the Special Issue entitled 'GABAergic Signaling in Health and Disease'. (C) 2014 Elsevier Ltd. All rights reserved.