Figure 4.

Pharmacologic studies confirmed that α5GABA_ARs are critical for the induction of LTP after moderate-frequency but not high-frequency stimulation. Recording of fEPSPs under control conditions was followed by application of L-655,708 for 10 min before (A) or immediately after (B) 10 Hz stimulation. Application of L-655,708 before but not after 10 Hz stimulation enhanced the fEPSPs of WT slices, which suggests that α5GABA_ARs are critical for the induction of threshold LTP but not for maintenance of the response. C, We next measured overall involvement of GABA_ARs in the LTP of submaximal stimulation by blocking these receptors with the competitive antagonist bicuculline. Application of bicuculline to WT slices that had been stimulated at 10 Hz produced LTP that was indistinguishable from that observed in Gabra5^−/− slices but did not further enhance the LTP in Gabra5^−/−slices. D, Bicuculline further potentiated LTP in WT and Gabra5^−/− slices relative to drug-free conditions with 100 Hz stimulation, which suggests that GABA_ARs not containing the α5 subunit play an active role in LTP when the intensity of activation is increased. Black traces, Pretetanus baseline; blue and red traces, 60 min after tetanus in WT and Gabra5^−/−slices, respectively. Calibration: 0.5 mV, 10 ms.