Striatal Neurons Expressing D 1 and D 2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice

Sci Rep. 2017 Jan 27;7:41432. doi: 10.1038/srep41432.

Abstract

The loss of nigrostriatal dopamine neurons in Parkinson's disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D1/D2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D1 and D2 MSNs, D1/D2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D1/D2 MSNs, but also of D1 and D2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D1 and D2 MSNs, the extent of dendritic arborization of D1/D2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D1/D2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Spines / metabolism
  • Denervation*
  • Dopamine / metabolism*
  • Dynorphins / metabolism
  • Enkephalins / metabolism
  • Mice, Transgenic
  • Neostriatum / metabolism*
  • Neurons / metabolism*
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / pathology
  • Oxidopamine
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D2 / metabolism*
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / pathology

Substances

  • Enkephalins
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Dynorphins
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Dopamine

Grant support