Fig. 2: Pericyte-mediated capillary constriction and CBF decrease involve CaVs.
a, Laser speckle imaging in the barrel cortex of WT and AD mice; blue/red show low/high perfusion. Capillary perfusion (between large vessels) was reduced in AD. P value: unpaired t-test. b, Capillary diameters 0–5 µm from soma center of 1st–3rd order pericytes in vivo in WT or AD NG2-dsRed mice (FITC-dextran in blood). P values: WT versus WT+nim paired t-test, AD versus AD+nim Wilcoxon test. WT data are from Fig. 1. c, Nim raises CBF (laser Doppler) in mature WT and AD (NG2-dsRed) mice. WT data are from Fig. 1c. d, Left, mean (±s.e.m.) normalized CBF, capillary diameter and pericyte soma [Ca2+]i after i.v. nim in mature AD NG2-CreERT2-GCaMP5G mice. Bar graphs: nim reduces [Ca2+]i in 1st–3rd order pericytes and SMCs, evoking dilation and raising CBF. Bars include some data acquired before and after nim without the whole timecourse being defined. e, Time to half-peak change of [Ca2+]i or CBF in d. P value: unpaired t-test. f, Nim reduces [Ca2+]i (image; also shows dilation) and its fluctuations (middle: pre-nim trace starts 3,004 units above zero) in processes of 1st–3rd order pericytes (AD cortex in vivo: see Supplementary Video 2). Right bar graph: mean [Ca2+]i in processes in nim relative to baseline. P values in c,d,f from paired t-tests. g,h, Quantification of Ca2+ transients in 1st–3rd order pericyte processes and somata (2-Hz acquisition). g, [Ca2+]i traces in processes of WT and AD mice with and without nim. Bar charts: transient rates and amplitudes in somata and processes. h, Fraction of cell somata or processes with transient rates/30 s in different ranges. i,j, As g,h but for SMCs. k, Summary: Aβ accumulation raises Ca2+ transient rates and mean [Ca2+]i, evoking pericyte contraction, capillary constriction and reduced CBF; nim reverses these changes. P values in g (soma rate and amplitudes) and i are from Kruskal–Wallis test with Dunn’s multiple comparison test and in g (process rate) from one-way ANOVA with Dunnett’s multiple comparison test. P values are two-tailed. Error bars are s.e.m. nim, nimodipine.
