Figure 5.

CCK and SST cells displayed hyperactive membrane properties, but CR cells remained unchanged in early AD. (A,C) Intrinsic membrane response of CA1 CCK interneurons and SST interneurons recorded using whole-cell patch clamp electrodes in wild-type and App^NL-F/NL-F mice at 2 months of age. Both CCK and SST cells displayed hyperexcitable membranes at −65 mV in response to intracellular current injections (ranging from +200 to −200 pA). Red traces are the voltage response of the cells to +200 pA current injection. (B,D) Graphs illustrate the number of action potentials discharged with increasing current applied to CCK and SST cells recorded in wild-type and App^NL-F/NL-F mice. The firing of both interneurons was dramatically increased with increasing current injections in the AD model, which was also accompanied by an increase in input resistance and time-constant illustrating hyperexcitability in the AD model. (E) Intrinsic membrane response of CA1 CR interneurons recorded in 2-month wild-type and App^NL-F/NL-F mice, respectively. These showed passive responses to intracellular current injections (+200 to −200 pA) which culminated in single- or double-action potentials with current injection of +150 pA (black traces). Red traces are the voltage response of the cells to +200-pA current injection. There were no significant differences in the action potential discharge, input resistance, and time constants between the two age-matched mouse cohorts. (F) The input–output curves displayed a pseudolinear relationship between number of action potentials generated by adapting CR cells of healthy wild-type and App^NL-F/NL-F mice with increasing current injections. The membrane input resistance, action potential threshold, and time constants did not appear to be different between the two genotypes studied. A two-way ANOVA was performed with genotype and treatment as factors (α = 0.05), with a post hoc Sidak’s test for multiple comparisons. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, ^****P < 0.0001.