INVOLVEMENT OF POSTSYNAPTIC G-PROTEINS IN HIPPOCAMPAL LONG-TERM POTENTIATION

The possible involvement of postsynapic guanosine 5-triphosphate (GTP)-binding proteins (G proteins) in long-term potentiation (LTP) was studied in rat hippocampal slices, using whole-cell recording techniques. The inclusion of guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) or guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) in the recording pipette significantly reduced or abolished the baclofen-induced hyperpolarization of pyramidal neurons, which indicates uncoupling of the signal transduction from G protein-coupled receptors by these compounds. Both GDP-beta-S and GTP-gamma-S significantly attenuated the magnitude of LTP in the fimbria-CA3 synapses, but not in the mossy fiber-CA3 synapses. GTP-gamma-S did not attenuate LTP in the Schaffer-CA1 synapses. The effects of guanine nucleotide analogs on fimbrial LTP were reversed by postsynaptic depolarization during high frequency stimulation. These results suggest that postsynaptic G proteins may be involved in the generation of LTP in the fimbrial synapses, possibly by affecting membrane depolarization during high frequency afferent activation.