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

• Published in: Pflügers Archiv 2009-11, Vol.459 (1), p.131-141
• Main Authors: Chepkova, Aisa N., Fleischer, Wiebke, Kazmierczak, Thomas, Doreulee, Nanuli, Haas, Helmut L., Sergeeva, Olga A.
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Corpus Striatum - growth & development; Corpus Striatum - metabolism; Electrophysiology; Excitatory Amino Acid Agents - pharmacology; Glycine - analogs & derivatives; Glycine - pharmacology; Human Physiology; Long-Term Synaptic Depression - physiology; Mice; Mice, Inbred C57BL; Molecular Medicine; Neurology; Neuronal Plasticity - physiology; Neuroscience; Neurosciences; Receptor, Cannabinoid, CB1 - metabolism; Receptors; Receptors, N-Methyl-D-Aspartate - metabolism; Resorcinols - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Synaptic Transmission - physiology
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-009-0714-7

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 (LTD DHPG ) in the adult mouse striatum requiring NO synthesis downstream to cannabinoid CB1 receptor (CB1R) activation suggesting a dual role for LTD DHPG : neuroprotective by down-regulation of glutamatergic transmission and, under certain circumstances, neurotoxic by release of NO. We report now that LTD DHPG 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 LTD DHPG 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.