Pflügers Archiv - European Journal of Physiology

, Volume 459, Issue 1, pp 131–141

Developmental alterations of DHPG-induced long-term depression of corticostriatal synaptic transmission: switch from NMDA receptor-dependent towards CB1 receptor-dependent plasticity

Authors

  • Aisa N. Chepkova
    • Department of NeurophysiologyHeinrich-Heine-University
  • Wiebke Fleischer
    • Department of NeurophysiologyHeinrich-Heine-University
  • Thomas Kazmierczak
    • Department of NeurophysiologyHeinrich-Heine-University
  • Nanuli Doreulee
    • Department of NeurophysiologyHeinrich-Heine-University
  • Helmut L. Haas
    • Department of NeurophysiologyHeinrich-Heine-University
    • Department of NeurophysiologyHeinrich-Heine-University
Neuroscience

DOI: 10.1007/s00424-009-0714-7

Cite this article as:
Chepkova, A.N., Fleischer, W., Kazmierczak, T. et al. Pflugers Arch - Eur J Physiol (2009) 459: 131. doi:10.1007/s00424-009-0714-7

Abstract

In animal models of early Parkinson’s disease (PD), motor deficits are accompanied by excessive striatal glutamate release. Blockade of group I metabotropic glutamate receptors (mGluRs), endocannabinoid degradation and nitric oxide (NO) synthesis combats PD symptoms. Activation of group I mGluRs with the specific agonist 3,5-dihydroxyphenylglycine (DHPG) induces long-term depression of corticostriatal transmission (LTDDHPG) in the adult mouse striatum requiring NO synthesis downstream to cannabinoid CB1 receptor (CB1R) activation suggesting a dual role for LTDDHPG: neuroprotective by down-regulation of glutamatergic transmission and, under certain circumstances, neurotoxic by release of NO. We report now that LTDDHPG undergoes a developmental switch from N-methyl-D-aspartate (NMDA)-receptor-dependent/CB1R-independent to NMDA receptor-independent/CB1R-dependent plasticity with NO playing an essential role for LTDDHPG at all developmental stages. The gain in function of CB1R is explained by their developmental up-regulation evaluated with real-time reverse transcription-polymerase chain reaction. These findings are relevant for the pathophysiology and therapy of PD as they link the activation of group I mGluRs, endocannabinoid release, and striatal NO production.

Keywords

Postnatal developmentCorticostriatal plasticityGroup 1 metabotropic glutamate receptorsNMDA receptorCB1 receptorNitric oxide

Copyright information

© Springer-Verlag 2009