Figure 4. Calretinin (CR)-expressing interneurons are functionally restored by NAM of α5 subunit-containing GABAARs in AppNL-F/NL-Fmice. A, B) Whole-cell current-clamp recordings of spontaneous inhibitory/excitatory postsynaptic potentials (sIPSPs and sEPSPs) recorded in CR cells in CA1 of 12 month old wild-type andAppNL-F/NL-F mice, at membrane potentials of -60 mV in control conditions, and after bath-application of α5-SOP002 (red traces). The squares indicate where synaptic events have been enlarged and shown in the inserts. *Indicate, an usually high sIPSPs recorded in the AD model. C, D) Bar graphs show the average sIPSP and sEPSP amplitude and frequency at -60 mV in CR cells recorded in wild-type mice and the AppNL-F/NL-F mouse model. These data suggest a significantly enhanced amplitude and frequency of inhibition in the AD model, which was “normalised” to control values after bath- application of α5-SOP002. E) Paired recording obtained between two putative CR cells recorded in SR of CA1 in the AD model. The unitary IPSPs were not sensitive to zolpidem, reduced by α5-SOP002, and then enhanced by subsequent addition of diazepam, indicating α5 pharmacology. F) Line graphs show the average unitary IPSP amplitude and width at half amplitude change for each paired recording between 2 CR cells, in control, and after bath-application of zolpidem, α5-SOP002 and diazepam, recorded at -55 mV in AppNL-F/NL-F mouse model. * P<0.05, **P< 0.01, ***P < 0.001, ****P < 0.0001.