Fig. 3: Mid-capillary bed pericytes exert enhanced contractile tone in AD mice.
a, In vivo two-photon imaging of mid-capillary bed in the barrel cortex of a WT NG2-dsRed mouse with FITC-dextran in the blood. Lines in the inset show sites of diameter measurements (graph: nim has little effect in WT vessels) at a pericyte soma (red, 1) on a capillary of >3rd branch order from the nearest PA and 2nd branch order from the AV, and at the AV (2). b, Intravenous nim partially restores capillary diameter decreases at the soma of >3rd order pericytes in AD NG2-dsRed mice. Inset: capillary diameter as a function of branch order in WT and AD mice in the absence of nim. P values for WT versus WT+nim (pre-nim versus post-nim) and AD versus AD+nim are from (paired) Wilcoxon tests; those for WT versus AD are from unpaired Mann–Whitney tests. c, Nim reduces [Ca2+]i in the soma and processes of >3rd order pericytes in vivo in AD NG2-CreERT2-GCaMP5G mice (images, colored traces are for processes 1 and 2 on images; pre-nim traces start at 368 and 310 for 1 and 2; left bar graph shows mean normalized changes). Nim evokes capillary dilation at pericyte somata (right bar graph). d, Schematic of laser-evoked in vivo brain injury near >3rd order capillaries in the barrel cortex of WT NG2-CreERT2-GCaMP5G mice. e–g, Laser-evoked injury raises [Ca2+]i (e,f) and contracts >3rd order pericytes near their somata (e,g; see also Supplementary Video 4 and Extended Data Fig. 4b). Injury-evoked capillary constriction was attenuated away from pericyte somata (g, P values above bars compare bar means with unity). h, Brain injury induces capillary stalling of blood near pericyte somata. Transient and prolonged capillary blocks were seen as in top and bottom panels. P values are from paired t-tests in c,f, paired and unpaired t-tests in g and a Wilcoxon test in e,h. P values are two-tailed. Error bars are s.e.m. 2-P, two-photon; nim, nimodipine.
