A loss of hippocampal perineuronal nets produces deficits in dopamine system function: relevance to the positive symptoms of schizophrenia

Transl Psychiatry. 2013 Jan 15;3(1):e215. doi: 10.1038/tp.2012.145.

Abstract

Deficits in parvalbumin containing interneurons are a consistent observation in animal models and schizophrenia patients. These neurons are surrounded by chondroitin sulfate proteoglycans, forming perineuronal nets, thought to support the high firing frequencies observed in these neurons. A loss of perineuronal nets has been observed post mortem in human schizophrenia patients, however, whether this contributes to the symptoms of schizophrenia is not known. Here we directly examine the effects of chondroitinase ABC degradation of ventral hippocampal (vHipp) perineuronal nets, and demonstrate that this results in an enhanced hippocampal activity and significant increase in dopamine neuron population activity. In addition, chondroitinase-treated rats display an augmented locomotor response to amphetamine, consistent with the enhanced response to psychomotor stimulants observed in schizophrenia patients. Taken together, these data demonstrate that a loss of vHipp perineuronal nets is sufficient, in and of itself, to induce aberrant hippocampal and dopamine system function consistent with that observed in rodent models and schizophrenia patients.

Publication types

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

MeSH terms

  • Amphetamine / pharmacology
  • Analysis of Variance
  • Animals
  • Chondroitin ABC Lyase / pharmacology*
  • Chondroitin Sulfate Proteoglycans / analysis*
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Disease Models, Animal
  • Dopamine / analysis*
  • Dopamine / metabolism
  • Hippocampus
  • Immunohistochemistry
  • Interneurons / drug effects*
  • Male
  • Methylazoxymethanol Acetate / pharmacology*
  • Parvalbumins / analysis*
  • Rats
  • Rats, Sprague-Dawley
  • Schizophrenia / chemically induced
  • Schizophrenia / physiopathology*

Substances

  • Chondroitin Sulfate Proteoglycans
  • Parvalbumins
  • Methylazoxymethanol Acetate
  • Amphetamine
  • Chondroitin ABC Lyase
  • Dopamine