Fig. 1: CaVs generate tone in SMCs and 1st–3rd order pericytes in WT mice in vivo. | Nature Neuroscience

Fig. 1: CaVs generate tone in SMCs and 1st–3rd order pericytes in WT mice in vivo.

From: Inhibiting Ca2+ channels in Alzheimer’s disease model mice relaxes pericytes, improves cerebral blood flow and reduces immune cell stalling and hypoxia

Fig. 1

a, Barrel cortex of anesthetized intubated mouse: FITC-dextran (green) in blood, laser Doppler for CBF, tail cuff measures BP (created with BioRender). b, Left, imaging of FITC-dextran in PA and 1st order capillary before and after i.v. nim in NG2-dsRed mouse (arrows: pericytes). Right, diameters at dashed lines on left, and CBF. c, Nim raises CBF compared to vehicle (veh). P value: Mann–Whitney test. d, Normalized diameter of pial arteries/PAs and capillaries at 1st–3rd order pericytes (0–5 μm from soma center) after nim (schematic from Extended Data Fig. 1a). e, Nim-evoked change in 1st order capillary diameter is largest at pericyte somata. P value assesses if the line slope is non-zero. f, Left, specimen nim-evoked changes in BP and CBF. Right, mean CBF (1–2 points per animal with 1–2 Doppler probes) and BP (one point per animal) after i.v. nim. Shortest recording was 53 min, so this timepoint (t53) was plotted for all traces. g, In vivo two-photon images of 1st order capillary pericytes and pial artery SMCs expressing GCaMP5G and tdTomato in NG2-CreERT2-GCaMP5G mice. Yellow lines, capillary outer diameter; magenta arrow, nim-evoked [Ca2+]i drop in process. h, Left, normalized (mean ± s.e.m.) change in CBF, diameter of arterioles and capillaries and [Ca2+]i in SMCs and pericytes, after nim. Bar graphs: (left) nim-evoked fall in [Ca2+]i evoking (middle) vasodilation at 1st–3rd order pericytes and SMCs, facilitating (right) CBF increases in NG2-CreERT2-GCaMP5G mice (as in NG2-dsRed or WT mice: c,f). Bars include some data acquired before and after nim without the whole timecourse being defined. i, Time to half-peak change of [Ca2+]i or CBF for h. j, Left, nim reduces mean [Ca2+]i in the pericyte process (pre-/post-nim traces start ~2,500/2,000 units above zero, respectively). Right, mean [Ca2+]i in processes in nim relative to baseline. P values are from paired t-tests in d,f,h,j (for SMC and process [Ca2+]i, arteriole/artery diameter and CBF), Wilcoxon test in h (pericyte [Ca2+]i and diameter) and unpaired t-test in i. P values are two-tailed. Error bars: s.e.m. 2-P, two-photon; nim, nimodipine; Veh, vehicle.

Source data

Back to article page