Extended Data Figure 10. Reactive microglia in different neuroinflammatory and neurodegenerative conditions show a reduction in Entpd1 and P2ry12 expression that is associated with an A₁R-dependent increase in D1 neuron responses.

a-g, Changes in Entpd1 and P2ry12 gene expression are shown in: a, RNA extracted from whole striatum of 6-month old control mice and Q175 (Huntington’s disease) mice⁹³ (Entpd1: P=0.0001; P2ry12: P=0.004; n=8 mice, fold change and P-value provided in publication). b, RNA from FACS-sorted CD11b+/F4/80+ cortical and hippocampal microglia from 8.5-month old control and 5xfAD mouse model of Alzheimer’s Disease⁹⁴ (Entpd1: P=0.009; P2ry12: P=0.0035; n=5 mice, fold change and P-value provided in publication). c, RNA from FACS-sorted forebrain microglia from 10-month old control and APP/PS1 Alzheimer’s disease mouse model³⁹ (n=3 mice, Entpd1: P=0.038; P2ry12: P=0.023, unpaired two-tailed t-test). d, RNA from FACS-sorted FCRLS+ phagocytic and non-phagocytic microglia isolated after stereotaxic injection of apoptotic neurons³⁹ (n=4 mice, Entpd1: P<0.0001; P2ry12: P<0.0001, unpaired two-tailed t-test). e, FACS-sorted FCRLS⁺ microglia in 24-month old control mice or APP/PS1 Alzheimer’s disease mouse model. Plaque associated microglia were identified and sorted based on CLEC7A expression³⁹ (n=6 mice, Entpd1: P=0.01; P2ry12: P<0.0001, One-way ANOVA with Tukey’s post hoc test). f, Massively parallel single-cell RNA-seq (MARS-seq) from isolated homeostatic microglia and disease associated microglia (DAM) in 5xfAD mice Alzheimer’s disease mouse model⁹⁵ (Entpd1: P<0.0001; P2ry12: P<0.0001; n=8,016 cells from 3 WT and 3 AD mice, fold change and P-value provided in publication). g, FACS-sorted CD11b⁺CD45^int single microglia in control and LPS-injected mice (4mg/kg)⁹⁶ (Entpd1: P<0.0001; P2ry12: P<0.0001; n=477 microglia from saline injected mice and 770 microglia from LPS injected mice, fold change and P-value provided in publication). h, i, Bar graphs show increased seizure susceptibility to D1 agonist administration (SKF81297, 5mg/kg, i.p.) in LPS-injected (indicated doses, i.p.) (h) and 6-8-month old 5xfAD Alzheimer’s mice (i) that is prevented by co-administration of an A₁R agonist (CPA, 0.1mg/kg, i.p.) (h, n=10-22 male mice, P=0.032, Chi-squared test; i, n=5-10 mice per genotype, left, P=0.031, Fisher’s exact test with Yates correction; right, P=0.49, Fisher’s exact test with Yates correction). j, Scheme illustrating the model of microglia-mediated adenosine-controlled regulation of D1 neuron responses in the healthy striatum (left) and its potential dysfunction upon microglia activation during inflammatory and/or neurodegenerative diseases (right). All statistical tests are two-tailed; Data shown as mean± s.e.m.