Control of basal ganglia output by direct and indirect pathway projection neurons

J Neurosci. 2013 Nov 20;33(47):18531-9. doi: 10.1523/JNEUROSCI.1278-13.2013.


The direct and indirect efferent pathways from striatum ultimately reconverge to influence basal ganglia output nuclei, which in turn regulate behavior via thalamocortical and brainstem motor circuits. However, the distinct contributions of these two efferent pathways in shaping basal ganglia output are not well understood. We investigated these processes using selective optogenetic control of the direct and indirect pathways, in combination with single-unit recording in the basal ganglia output nucleus substantia nigra pars reticulata (SNr) in mice. Optogenetic activation of striatal direct and indirect pathway projection neurons produced diverse cellular responses in SNr neurons, with stimulation of each pathway eliciting both excitations and inhibitions. Despite this response heterogeneity, the effectiveness of direct pathway stimulation in producing movement initiation correlated selectively with the subpopulation of inhibited SNr neurons. In contrast, effective indirect pathway-mediated motor suppression was most strongly influenced by excited SNr neurons. Our results support the theory that key basal ganglia output neurons serve as an inhibitory gate over motor output that can be opened or closed by striatal direct and indirect pathways, respectively.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Basal Ganglia / cytology*
  • Channelrhodopsins
  • Electric Stimulation
  • Locomotion / physiology*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition / physiology
  • Neural Pathways / physiology*
  • Neurons / physiology*
  • Optogenetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Receptors, Adenosine A2 / genetics
  • Receptors, Dopamine D1 / genetics
  • Substantia Nigra / cytology


  • Bacterial Proteins
  • Channelrhodopsins
  • Luminescent Proteins
  • Proto-Oncogene Proteins c-fos
  • Receptors, Adenosine A2
  • Receptors, Dopamine D1
  • yellow fluorescent protein, Bacteria