Effects of GABAergic disinhibition on the long-term potentiation at CA1 hippocampal synapses

Abstract

Objective To investigate the effects of GABAergic inhibition medicated by the interneurons on the induction of long-term potentiation （LPT）, and determine the concentration of bicuculline required to block GABAA receptor-mediated inhibition and affect LTP induction at CA1 hippocampal synapse. Methods Using whole-cell recording technique, the mini-inhibitory postsynaptic current （mlPSC） and evoked feedforward inhibitory post synaptic current （IPSC） were measured from the CA1 neurons in the hippocampal slices. Extracellular recording of field excitatory postsynaptic potential （fEPSP） by Schaffer collateral stimulation was used to study the synaptic plasticity in adult mice hippocampal slices, and the effects of bicuculline at different concentrations on mlPSC, IPSC, fEPSP and LTP induction were evaluated. Results Bicuuclline at 10 and 20 μmol/L abolished mlPSC and IPSC currents. The action of 20 μmol/L bicuucUine were more obviously. The slope of fEPSPs were significantly enhanced by application of bicuculline at 20 μmol/L, but not at 5 or 10 μmol/L. In the presence of 5, 10, 20 and 50 μmol/L bicuculline, LTP of the fEPSP slope following 100 Hz tetanization was enhanced, but the increment was significant only for 10 and 20 μmol/L bicuculline （P〈0.05）. Conclusion Bicuculline can abolish GABAA receptor-mediated inhibition and affect the excitatory postsynaptic potential in a dose-dependent manner, and at a critical level, bicuculline induces GABAergic disinhibition to result in enhanced LTP in hippocampal slices. Key words: Hippocampus; Synaptic plasticity; GABAA receptor; Long-term potentiation