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Neuropharmacology. 2015 Jan;88:24-35. doi: 10.1016/j.neuropharm.2014.08.003. Epub 2014 Aug 13.

Altered expression of δGABAA receptors in health and disease.

Author information

1
Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
2
Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
3
Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, M5S 1A8, Canada; Department of Anesthesia, Sunnybrook Health Sciences Centre, Toronto, Ontario, M4N 3M5, Canada. Electronic address: beverley.orser@utoronto.ca.

Abstract

γ-Aminobutyric acid type A receptors that contain the δ subunit (δGABAA 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, δGABAA 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 δGABAA 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 δGABAA receptors associated with various states of health and disease and the implications of these changes.

KEYWORDS:

Behavior; Disease; Expression; Plasticity; Tonic inhibition; δGABA(A) receptor

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