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.