Fig. 1: Rapid stimulation of astrocytes modulates striatal DA release via ACh.
From: Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes
a, f, k, r Viral expression, mouse line and recording paradigms. b Striatal astrocyte expressing GFAP-ChR2-EYFP (green), DAPI (blue), and S100β-immunoreactivity (red). Scale, 20 µm. c Top, differential interference contrast (DIC) image and bottom, EYFP epifluorescent image, of ChR2-EYFP astrocyte. Scale, 20 µm. d, e Example astrocyte membrane voltage (Vm) responses to (d) current injections (Iinj) or (e) blue light (~4–5 mW) for 5 ms (top) or 50 ms (bottom). g Mean [DA]o transients evoked by one electrical pulse (Estim) without prior light or after light (blue bar, 500 ms) in GFAP-ChR2-expressing (left) versus mCherry-expressing controls (right). h, m Mean peak [DA]o ± SEM evoked by 1p with and without blue light stimulation (blue column) in GFAP-ChR2-expressing (dark blue) versus mCherry controls (gray), normalized to pre-light baseline (dotted line) in (h) DLS (ChR2: n = 17(12), mCherry: n = 8(5)), or (m) NAcc (ChR2: n = 9(5), mCherry: n = 6(4)). Trials in which DA release was observed at light onset (l, right) were not included in averages. i–j, n, o Ratio of peak [DA]o evoked by 5p (50 Hz) versus 1p with and without light activation for ChR2 (i, n) and mCherry (j, o) in DLS (i, j), or NAc (n, o). ChR2: n = 17(12), mCherry: n = 8(5). l Left: Mean [DA]o transients evoked in NAc by 1p (Estim) with or without light (blue bar, 500 ms). Right: As left, but example light evoking DA release. p As (h), but with DHβE (1 µM; gray). Drug-free: n = 17(12), DHβE: n = 9(6). q Ratio of peak [DA]o evoked by 5p (50 Hz):1p with and without light-activation with ChR2-expression and DHβE. Drug-free: n = 17(12), DHβE: n = 9(6). s Mean peak [DA]o evoked by 1p and (t) 5p:1p ratio, with/without blue light (blue column) during CNO application (1 µM) in GFAP-ChR2 mice with expression of hM4Di-mCherry (gray) (n = 5(3)) or mCherry controls (yellow) (n = 5(3)), normalized to pre-light baseline. ***p < 0.001; **p < 0.01; *p < 0.05. Repeated measures ANOVA in (h), (m), (p), (s); Wilcoxon rank sort test in (q); paired two-sided t test in (i), (j), (n), (o), (t). Error bars denote s.e.m. Source data are provided in a Source Data file. Cartoon cell components created in BioRender. Cragg, S. (2023) BioRender.com/k30f956. Cragg, S. (2024) BioRender.com/p68j108.
