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

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


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basal Ganglia / physiology*
  • Mice, Transgenic
  • Models, Neurological
  • Neural Pathways / physiology*
  • Neurons / physiology*
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism


  • Receptors, Dopamine D1
  • Receptors, Dopamine D2