Changes to interneuron-driven striatal microcircuits in a rat model of Parkinson's disease

Neurobiol Dis. 2009 Jun;34(3):545-52. doi: 10.1016/j.nbd.2009.03.006. Epub 2009 Mar 31.

Abstract

Striatal interneurons play key roles in basal ganglia function and related disorders by modulating the activity of striatal projection neurons. Here we have injected rabies virus (RV) into either the rat substantia nigra pars reticulata or the globus pallidus and took advantage of the trans-synaptic spread of RV to unequivocally identify the interneurons connected to striatonigral- or striatopallidal-projecting neurons, respectively. Large numbers of RV-infected parvalbumin (PV+/RV+) and cholinergic (ChAT+/RV+) interneurons were detected in control conditions, and they showed marked changes following intranigral 6-hydroxydopamine injection. The number of ChAT+/RV+ interneurons innervating striatopallidal neurons increased concomitant with a reduction in the number of PV+/RV+ interneurons, while the two interneuron populations connected to striatonigral neurons were clearly reduced. These data provide the first evidence of synaptic reorganization between striatal interneurons and projection neurons, notably a switch of cholinergic innervation onto striatopallidal neurons, which could contribute to imbalanced striatal outflow in parkinsonian state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calbindin 2
  • Cell Count
  • Choline O-Acetyltransferase / metabolism
  • Densitometry
  • Disease Models, Animal
  • Globus Pallidus / physiopathology*
  • Immunohistochemistry
  • Interneurons / physiology*
  • Male
  • Nitric Oxide Synthase Type I / metabolism
  • Oxidopamine
  • Parkinson Disease / physiopathology*
  • Parvalbumins / metabolism
  • Rabies virus
  • Rats
  • Rats, Wistar
  • S100 Calcium Binding Protein G / metabolism
  • Substantia Nigra / physiopathology*

Substances

  • Calbindin 2
  • Parvalbumins
  • S100 Calcium Binding Protein G
  • Oxidopamine
  • Nitric Oxide Synthase Type I
  • Choline O-Acetyltransferase