Stephen J. Moss Laboratory

Research Interests

The fast inhibitory (milliseconds) action of GABA in the mammalian brain is largely mediated by GABA_Α receptors, which are chloride selective ligand-gated ion channels. Their activation in adult brain results in neuronal hyperpolarization. GABA_Α receptors are also the sites of action for benzodiazepines, barbiturates, neurosteroids and general anesthetics, which all act to potentiate receptor activity together and affect the efficacy of inhibitory synaptic transmission. Compromised GABA_Α receptor function is significant in a number of CNS disorders including: epilepsy, anxiety, sleep disorders, addiction, autism and mental retardation.

The slow inhibitory actions (seconds to minutes) of GABA are mediated by GABA_Β receptors which are G-protein coupled receptors (GPCRs). Postsynaptically GABA_Β receptors activate inwardly-rectifying K⁺ channels leading to neuronal hyper-polarization while presynaptically they inactivate voltage-gated Ca²⁺ channels, decreasing neurotransmitter release. GABA_Β receptors also inhibit adenylate cyclase leading to diminished activity of PKA signaling pathways. Compromised GABA_Β receptor function is significant in epilepsy and has been strongly implicated in depression, neuropathic pain, addiction and feeding behavior.

Given the critical role that GABA receptors play in synaptic inhibition, as drug targets and in human pathology it is of fundamental importance to understand how neurons regulate their accumulation on the surface of neurons and their functional properties. To address these issues we use a combination of biochemical, cell biological, electrophysiological, genetic and pharmacological experimental approaches to detail these endogenous mechanisms for GABA_Α and GABA_Β receptors respectively.

Last Updated: 04-May-2006