Gamma amino buteric acid (GABA) is the principal inhibitory neurotransmitter in the brain. GABA excerts its action though specific receptors that are ionotropic, permeable to chloride and bicarbonate (GABA A receptors) and G-protein coupled receptors (GABA B receptors).

We have  previously described the activation kinetics of GABA B receptors [refs], but the present focus of our research is the activation and modulation of ionotropic GABA A receptors. These receptors can be divided into those localized at synapses and those found preferentially outside synaptic contacts. The former constitute a variety of GABA A receptor subunit assemblies, but the latter are restricted to less than a handful of specific subunit assemblies. These latter receptors contain specific subunit combinations that can be altered in disease (Brickley and Mody, 2012). Our goal is to delineate specific alterations in synaptic and extrasynaptic GABA A receptors in neurologic (Clarkson AN, 2010) and psychiatric disorders (Maguire 2005). Our work on a mouse model of postpartum depression (Maguire and Mody, 2008) has led to the development of a synthetic allopregnanolone derivative (Kanes S, 2017) for the treatment of this disorder in women after giving birth. We are also interested in a specific form of neuronal plasticity called ‘ionic plasticity’ at GABA A receptors that is dependent on the dynamic regulation of intracellular Cl,locally in neuronal compartments. This plasticity is unique to Cl dependent inhibitory transmission and it appears to be one of the key factors responsible for altered neuronal plasticity in aging (Ferando, I, 2016).

Current projects at the Modylab involving the actions of GABA in the brain

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