Home » The role of the gamma-aminobutyric acid type A receptor in learning and memory. by Melissa Dawn Moore
The role of the gamma-aminobutyric acid type A receptor in learning and memory. Melissa Dawn Moore

The role of the gamma-aminobutyric acid type A receptor in learning and memory.

Melissa Dawn Moore

Published
ISBN : 9781109144840
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107 pages
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The gamma-aminobutyric acid type A receptor (GABA AR) is a heteropentameric ligand-gated ion channel that mediates rapid inhibition in the mammalian central nervous system. The GABAAR is the target of a wide variety of clinically relevant allostericMoreThe gamma-aminobutyric acid type A receptor (GABA AR) is a heteropentameric ligand-gated ion channel that mediates rapid inhibition in the mammalian central nervous system. The GABAAR is the target of a wide variety of clinically relevant allosteric modulators, such as benzodiazepines, barbiturates, anesthetics, neurosteroids, and ethanol. The affinity/efficacy of these agonists depends on developmental stage, brain region, synaptic location and, most importantly, the specific isoform of the GABAAR. Of particular interest to this dissertation is the GABA AR subtype alpha4betadelta, due to its high sensitivity to very low levels of ethanol and neurosteroids. In this dissertation, we report that a global loss of the GABAAR alpha4 subunit enhances hippocampus-dependent fear conditioning in GABAAR alpha4 knockout mice in a sex-dependent manner, utilizing both trace and delay fear conditioning behavioral assays. In an effort to further probe the interaction of the GABAAR alpha4 subunit and ethanol in learning and memory, we first developed a low dose ethanol assay. In wild-type C57B1/6 mice, we found that 1.0 g/kg ethanol blocks the context pre-exposure rescue of the immediate shock deficit and this is reversed by the GABAAR behavioral antagonist Ro15-4513. Furthermore, we argue against an indirect action of ethanol at the GABAAR, as Ro15-4513 was unable to reverse the ALLO-mediated impairment of the pre-exposure facilitation of the immediate shock deficit. Taken as a whole, this work lays the foundation for further investigation into the role of the GABAAR alpha4 subunit in learning and memory.