biostudies-literatureLee HJNIBIB NIH HHSNIA NIH HHSNINDS NIH HHSNIH HHS412-24https://www.ebi.ac.uk/biostudies/studies/S-EPMC5528162biostudies-literatureUnknown91(2)A central theory of basal ganglia function is that striatal neurons expressing the D1 and D2 dopamine receptors exert opposing brain-wide influences. However, the causal influence of each population has never been measured at the whole-brain scale. Here, we selectively stimulated D1 or D2 receptor-expressing neurons while visualizing whole-brain activity with fMRI. Excitation of either inhibitory population evoked robust positive BOLD signals within striatum, while downstream regions exhibited significantly different and generally opposing responses consistent with-though not easily predicted from-contemporary models of basal ganglia function. Importantly, positive and negative signals within the striatum, thalamus, GPi, and STN were all associated with increases and decreases in single-unNeuronActivation of Direct and Indirect Pathway Medium Spiny Neurons Drives Distinct Brain-wide Responses.PMC5528162DP2 OD007265R00 EB008738R01 NS091461R01 NS087159R01 NS064984RF1 AG047666Kreitzer ACKravitz AVBernal-Casas DLee HJWeitz AJDuffy BAChoy MLee JHfalseActivation of Direct and Indirect Pathway Medium Spiny Neurons Drives Distinct Brain-wide Responses.A central theory of basal ganglia function is that striatal neurons expressing the D1 and D2 dopamine receptors exert opposing brain-wide influences. However, the causal influence of each population has never been measured at the whole-brain scale. Here, we selectively stimulated D1 or D2 receptor-expressing neurons while visualizing whole-brain activity with fMRI. Excitation of either inhibitory population evoked robust positive BOLD signals within striatum, while downstream regions exhibited significantly different and generally opposing responses consistent with-though not easily predicted from-contemporary models of basal ganglia function. Importantly, positive and negative signals within the striatum, thalamus, GPi, and STN were all associated with increases and decreases in single-un2016-01-01T00:00:00Z2016 Jul2026-05-05T20:46:37.901Z2019-03-27T02:51:41ZS-EPMC55281622737383410.1016/j.neuron.2016.06.010