Functional and molecular heterogeneity of D2R neurons along dorsal ventral axis in the striatum

Nat Commun. 2020 Apr 23;11(1):1957. doi: 10.1038/s41467-020-15716-9.

Abstract

Action control is a key brain function determining the survival of animals in their environment. In mammals, neurons expressing dopamine D2 receptors (D2R) in the dorsal striatum (DS) and the nucleus accumbens (Acb) jointly but differentially contribute to the fine regulation of movement. However, their region-specific molecular features are presently unknown. By combining RNAseq of striatal D2R neurons and histological analyses, we identified hundreds of novel region-specific molecular markers, which may serve as tools to target selective subpopulations. As a proof of concept, we characterized the molecular identity of a subcircuit defined by WFS1 neurons and evaluated multiple behavioral tasks after its temporally-controlled deletion of D2R. Consequently, conditional D2R knockout mice displayed a significant reduction in digging behavior and an exacerbated hyperlocomotor response to amphetamine. Thus, targeted molecular analyses reveal an unforeseen heterogeneity in D2R-expressing striatal neuronal populations, underlying specific D2R's functional features in the control of specific motor behaviors.

Publication types

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

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Biomarkers / metabolism
  • Corpus Striatum / cytology
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiology
  • Dopamine Agents / pharmacology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Neostriatum / cytology*
  • Neostriatum / metabolism
  • Neostriatum / physiology
  • Neural Pathways
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology*
  • Nucleus Accumbens / cytology*
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiology
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*

Substances

  • Biomarkers
  • DRD2 protein, mouse
  • Dopamine Agents
  • Membrane Proteins
  • Receptors, Dopamine D2
  • wolframin protein
  • Amphetamine