Figure 6.

α5GABA_ARs regulate membrane properties and the depolarizing envelope to set the threshold for long-term potentiation within the 10 Hz stimulation range. A, The membrane potential was significantly depolarized in α5 null mutant (Gabra5^−/−) and L-655,708-treated WT neurons during 10 Hz stimulation. The average membrane potential for the 10 min period after 10 Hz stimulation was significantly hyperpolarized from baseline values in WT. All recordings were conducted in the presence of SR-95531 and CGP 55845 to block synaptic GABA_A and GABA_B receptors, respectively. The membrane potential during and after 10 Hz stimulation were compared with baseline membrane potentials for the respective treatments. B, Sample traces show the membrane hyperpolarizing pulse for WT, Gabra5^−/−, and L-655,708-treated WT neurons, before and 30 min after 10 Hz stimulation. The average input resistance was significantly decreased in WT but not Gabra5^−/− or L-655,708-treated WT neurons. The individual changes in input resistance for each cell are shown in the “before” and “after” plots. Colored symbols represent the group means. 1, Baseline EPSP; 2, EPSP 30 min after 10 Hz stimulation. C, Sample traces show that, during 10 Hz stimulation, the EPSPs were significantly smaller, for the duration of the simulation period, in WT neurons than in Gabra5^−/− and L-655,708-treated WT neurons. Insets show that the EPSPs were larger for Gabra5^−/− and L-655,708-treated WT neurons near the beginning and at the end of the stimulation period. D, Pooled data show that the average depolarizing envelope was significantly larger in Gabra5^−/− neurons and L-655,708-treated WT neurons than in WT control neurons. E, Examples of EPSP responses for single WT (blue), Gabra5^−/− (red), and L-655,708-treated WT (gray) neurons. 1, Baseline EPSP; 2, EPSP 30 min after 10 Hz stimulation. Calibration: 4 mV, 10 ms. F, Summary of the EPSP changes after 10 Hz stimulation for all groups. *p < 0.05.