Fig. 4: Adult-onset human APP expression does not alter excitatory neuron physiology.

a Graphical summary of AAV.EF1a.hAPP (or for Ctrl, saline) stereotactic injection in the Lateral Entorhinal Cortex. Excitatory cells were targeted for whole-cell current clamp recordings. b AP firing elicited by square pulse current injections of varying magnitude normalized to cellular capacitance during recording in Ctrl and hAPP injected L2 LEC excitatory cells from at 12 pA/pF. c Group data summary of AP firing frequency in L2 LEC from Ctrl (black) and hAPP injected mice (magenta). Excitatory neurons in L2 LEC from hAPP injected mice show no alteration in AP Frequency (Hz) when compared to Ctrl (Ctrl: Max: 50.42 ± 5.63 Hz, hAPP: Max: 59.43 ± 6.56 Hz, p = 0.99, df = 28). d Summary data of AP properties. L2 LEC excitatory cells after hAPP injection display an unchanged Membrane Capacitance (p = 0.83, t = 0.27, Ctrl: minimum: 77.13, 25% percentile: 189.5, median: 208.5, 75% percentile: 261.9, maximum: 377.5, range: 300.3; hAPP: minimum: 103.0, 25% percentile: 189.9, median: 226.4, 75% percentile: 281.1, maximum: 324.4, range: 221.3) as well as an unchanged input resistance (p = 0.15, t = 1.50, df = 28; Ctrl: minimum: 30.98, 25% percentile: 60.00, median: 85.43, 75% percentile: 122.9, maximum: 259.8, range: 228.9; hAPP: minimum: 40.70, 25% percentile: 41.29, median: 59.46, 75% percentile: 106.4, maximum: 146.2, range: 105.5), data points represent biological replicates; Ctrl n = 19, hAPP n = 11. e Graphical summary of AAV.EF1a.hAPP (or for Ctrl, saline) stereotactic injection in the Somatosensory Cortex. Excitatory neurons in L5 were targeted for whole-cell current clamp recordings. f AP firing elicited by square pulse current injections of varying magnitude normalized to cellular capacitance during recording in excitatory cells from L5 SS Ctx at 12 pA/pF. g Group data summary of AP firing frequency in L5 SS Ctx from Ctrl (black) and hAPP injected mice (magenta). SS Ctx excitatory neurons from hAPP injected mice show no significant change in AP Frequency (Hz) when compared to Ctrl (Ctrl: Max: 46.35 ± 5.38 Hz, hAPP: Max: 61.43 ± 6.78 Hz, p > 0.05, df = 40). h Summary data of AP properties. SS Ctx interneurons after hAPP injection display an unchanged Membrane Capacitance (Ctrl: 176.9 ± 11.58, hAPP: 140.5 ± 14.31, p = 0.06, t = 1.98, df = 40, two-tailed unpaired t-test; Ctrl: minimum: 63.66, 25% percentile: 141.4, median: 180.5, 75% percentile: 229.4, maximum: 248.3, range: 184.7; hAPP: minimum: 47.71, 25% percentile: 88.57, median: 127.2, 75% percentile: 191.3, maximum: 285.2, range: 237.5) and input resistance (Ctrl: 117.8 ± 8.93, hAPP: 140.5 ± 20.43, p = 0.23, t = 1.05, df=40, two-tailed unpaired t-test; Ctrl: minimum: 58.62, 25% percentile: 91.03, median: 117.1, 75% percentile: 145.8, maximum: 202.1, range: 143.5; hAPP: minimum: 39.12, 25% percentile: 54.81, median: 111.9, 75% percentile: 215.4, maximum: 326.2, range: 287.5) data points represent biological replicates; Ctrl n = 21, hAPP n = 21. i RNAscope representative images at 40x magnification for Ctrl injected (top) and hAPP injected mice (bottom(: mAPP mRNA (cyan), CaMKIIa mRNA (green), human APP mRNA (magenta), and a final merged image. j RNAscope quantification for hAPP copies per CaMKIIa+ cell comparing control to hAPP injected. hAPP injected show a significant increase in hAPP copies per CaMKIIa+ cell (p = 0.0007, t = 7.42, df = 5; two-tailed paired t-test). For all summary graphs, data are expressed as mean ( ± SEM). For c, g Statistical significance is denoted as *p < 0.05, as determined by Two-way ANOVA with Sidak’s multiple comparison test. For d, h Individual data points and box plots are displayed. Statistical significance is denoted as *p < 0.05, as determined by two-tailed unpaired t-test. Source data are provided as a Source Data File.