The developmental onset of NMDA receptor-channel activity during neuronal migration

David J. Rossi, N. Traverse Slater

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

Patch-clamp recordings of granule cells in thin slices of developing rat cerebellum maintained in vitro displayed spontaneous single-channel activity mediated via activation of N-methyl-d-aspartate (NMDA) receptors. The frequency of tonic single-channel activity was reversibly inhibited by the NMDA receptor/channel antagonists d-2-amino-5-phosphonovalerate (d-AP5), 7-chloro-kynurenate (7-Cl-Kynu) and MgCl2, potentiated by glycine, and unaffected by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or tetrodotoxin (TTX). Tonic channel activity was also reversibly inhibited by enzymatic degradation of endogenous glutamate by glutamate pyruvate transaminase, which did not affect the NMDA sensitivity of granule cells. Both the frequency of spontaneous channel activity and the NMDA sensitivity were low in premigratory cells of the external germinal layer (EGL), with large increases observed in migrating cells in the molecular layer (ML) and in postmigratory cells within the internal granule cell layer (GCL). Tonic channel activity was enhanced by the glutamate uptake inhibitor l-α-aminoadipate (l-α-AA), the degree of enhancement being greater in the EGL than the GCL. The results demonstrate that a dramatic increase in the tonic NMDA receptor-channel activity occurs during the stages of granule cell differentiation, migration and synaptogenesis, which is driven by endogenous glutamate release and regulated by NMDA receptor density and local glutamate uptake.

Original languageEnglish (US)
Pages (from-to)1239-1248
Number of pages10
JournalNeuropharmacology
Volume32
Issue number11
DOIs
StatePublished - Nov 1993

Keywords

  • NMDA
  • calcium
  • cerebellum
  • granule cells
  • migration
  • patch-clamp

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'The developmental onset of NMDA receptor-channel activity during neuronal migration'. Together they form a unique fingerprint.

  • Cite this