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Neuron. 2016 Jul 20;91(2):412-24. doi: 10.1016/j.neuron.2016.06.010. Epub 2016 Jun 30.

Activation of Direct and Indirect Pathway Medium Spiny Neurons Drives Distinct Brain-wide Responses.

Author information

1
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
2
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
3
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.
4
Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
5
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.

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.

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PMID:
27373834
PMCID:
PMC5528162
DOI:
10.1016/j.neuron.2016.06.010
[Indexed for MEDLINE]
Free PMC Article

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