Acute ethanol administration impairs spatial memory in both rats and mice. Specifically, ethanol administration impairs the use of spatial memory, spatial learning and blocks spatial contextual learning. Furthermore, the cellular mechanism underlying acute ethanol's impairment of spatial memory has been identified. Namely, acute ethanol administration degrades the spatial specificity of hippocampal place cells recorded in awake freely behaving rats. However, the biochemical mechanism by which acute ethanol administration impairs spatial memory is unknown. Ethanol potentiates GABA-mediated inhibition in a variety of brain regions including brain regions in the hippocampal system. Hence, ethanol might impair spatial memory by potentiating GABA-mediated inhibition in these brain regions thereby altering hippocampal function. However, it is still controversial if ethanol interacts directly with GABAA receptors in brain. The goal of this proposal is to directly investigate if targeted genetic alteration in the gamma2 subunit of the GABAA receptor alters ethanol degradation of spatial memory. GABAA receptor gamma2 heterozygous knockout mice (expressed on the hybrid C57B1/6J - 129/SvJ strain) will be trained a variety of spatial tasks prior to having 1) their spatial memory tested or 2) the spatial specificity of hippocampal place cells determined following administration of one of three doses of ethanol (saline control, 1.25 g/kg, 1.75 g/kg or 2.25 g/kg) or diazepam (1.0 mg/kg, 1.5 mg/kg or 2.0 mg/kg). These studies will directly determine if alterations in GABAA receptor composition via targeted genetic alteration in the gamma2 subunit of the GABAA receptor alter ethanol impairment of spatial memory.
| Berry, Raymond B; Chandra, Dev; Diaz-Granados, Jaime L et al. (2009) Investigation of ethanol-induced impairment of spatial memory in gamma2 heterozygous knockout mice. Neurosci Lett 455:84-7 |
| Berry, Raymond B; Werner, David F; Wang, Xiaofei et al. (2008) Mice with targeted genetic reduction of GABA(A) receptor alpha1 subunits display performance differences in Morris water maze tasks. Neurobiol Learn Mem 90:580-3 |
