Figure 5.
The neurosteroid alphaxalone markedly increases GABAergic IPSC decay times in both WT and β3N265M knock-in Pef, TMN, and LC neurons. The main traces in each panel shows the effects of alphaxalone on the cumulative probability distributions of IPSC decay times averaged across all recorded neurons under control conditions (black curve) and during exposure to 2 μm alphaxalone (red curve). The lighter lines show the SEMs. The insets show representative average IPSCs (normalized to peak amplitude) from individual neurons. A, The cumulative decay time distributions for Pef neurons from both WT and β3N265M knock-in mice show clear, and comparable, rightward shifts in the presence of alphaxalone (for WT neurons, τ increased by 175 ± 30%, n = 5, and for β3N265M neurons, τ increased by 159 ± 30%, n = 4). Data from a typical WT Pef neuron (left inset), shows a large increase in the average IPSC decay time from 17 ms (n = 51) for control, to 53 ms (n = 81) in the presence of alphaxalone. Data from a typical β3N265M Pef neuron (right inset) shows a similar increase from 16 ms (n = 51) to 40 ms (n = 105). B, The cumulative decay time distributions for TMN neurons from both WT and β3N265M knock-in mice show clear, and comparable, rightward shifts (for WT neurons, τ increased by 188 ± 30%, n = 5, and for β3N265M neurons, τ increased by 178 ± 41%, n = 4). Data from a typical WT TMN neuron (left inset), shows a large increase in the average IPSC decay time from 24 ms (n = 63) for control to 71 ms (n = 49) in the presence of alphaxalone. Data from a typical β3N265M TMN neuron (right inset) shows a similar increase from 21 ms (n = 50) to 82 ms (n = 48). C, The cumulative decay time distributions for LC neurons from both WT and β3N265M knock-in mice show clear, and comparable, rightward shifts (for WT neurons, τ increased by 149 ± 15%, n = 8, and for β3N265M neurons, τ increased by 154 ± 26%, n = 6). Data from a typical WT LC neuron (left inset), shows a large increase in the average IPSC decay time from 27 ms (n = 127) for control to 52 ms (n = 71) in the presence of alphaxalone. Data from a typical β3N265M LC neuron (right inset) shows a similar increase from 29 ms (n = 59) to 78 ms (n = 47).