Extended Data Fig. 2: Early functional alterations in the AppNL-G-F mice. | Nature Neuroscience

Extended Data Fig. 2: Early functional alterations in the AppNL-G-F mice.

From: Early alterations in the MCH system link aberrant neuronal activity and sleep disturbances in a mouse model of Alzheimer’s disease

Extended Data Fig. 2: Early functional alterations in the AppNL-G-F mice.

a,b,c,d Whole-cell current clamp recordings of intrinsic properties from CA1 pyramidal neurons from Wt and AppNL-G-F at different months (MO). (a) Intrinsic excitability, firing rate in function of somatic current injection, (b) resting membrane potential, (c) Tau membrane constant and (d) input resistance. Number of neurons from 3 or more mice, 3MO - Wt n = 14, AppNL-G-F n = 20; 4MO - Wt n = 11, AppNL-G-F n = 12, 6MO - Wt n = 11, AppNL-G-F n = 17. Two-tailed unpaired t-test. (*p < 0.05). (a) Two-way ANOVA, with Holm-Sidak post-hoc multiple comparisons test (190 pA p = 0.0157, 210 pA p = 0.0098, 230 pA p = 0.0018, 250 and 270 pA p = 0.0008, 290 pA p = 0.0171, 310 pA p = 0.0212, 330 pA p = 0.0303)). (b,c,d) Two-tailed unpaired t-test. Individual data points shown with bars representing mean ± SEM. (*p < 0.05, **p < 0.01, ***p < 0.001). e, Images of Wt (left) and AppNL-G-F (right) acute hippocampal slices on the multielectrode array (MEA2100, Multichannel Systems) used for field excitatory postsynaptic potential (fEPSP) recordings. Stimulation and recording electrodes are indicated with purple and yellow circles, respectively. f, Example traces of fEPSP responses in Wt and AppNL-G-F before (dark traces) and 55 minutes after minimal LTP induction (light traces). g, LTP induced in CA1 region by Schaffer collateral (SC) pathway stimulation using 3 theta burst stimulations. h, LTP induced in CA1 region using minimized theta burst stimulation paradigm (65.05 min p = 0.048, 81.55 min p = 0.049, 92.55 min p = 0.0366). i, Input-output (IO) relationship for Wt and AppNL-G-F slices. j, Paired-pulse ratio (PPR) stimulations of SC pathway. Stimulation intensities used for LTP and paired pulse ratio recordings were calculated from CA1 region using SC stimulation in Wt and AppNL-G-F slices (inter stimulus intervals (ISI): 25, 50, 100, 200 and 400 ms). Number of mice: Normal LTP –Wt n = 5, AppNL-G-F n = 5; Minimal LTP - Wt n = 4, AppNL-G-F n = 4. Two-way ANOVA, with Holm-Sidak post-hoc multiple comparisons test. Individual data points shown with bars representing mean ± SEM. (*p < 0.05).

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