title: Activation of Direct and Indirect Pathway Medium Spiny Neurons Drives Distinct Brain-wide Responses.
abstract: 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-unit activity, respectively. These findings provide direct evidence for the opposing influence of D1 and D2 receptor-expressing striatal neurons on brain-wide circuitry and extend the interpretability of fMRI studies by defining cell-type-specific contributions to the BOLD signal.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Weitz
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: David
authors.initials: D
authors.lastname: Bernal-Casas
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Duffy
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: ManKin
authors.initials: M
authors.lastname: Choy
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA; Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Alexxai V
authors.initials: AV
authors.lastname: Kravitz
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Anatol C
authors.initials: AC
authors.lastname: Kreitzer
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA. Electronic address: ljinhy@stanford.edu.
authors.forename: Jin Hyung
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D008822:Mice, Transgenic; D008959:Models, Neurological; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2