Splice-specific roles of glycine receptor alpha3 in the hippocampus

Autor/innen

  • S.A. Eichler
  • B. Foerstera
  • B. Smolinsky
  • R. Juettner
  • T.N. Lehmann
  • M. Faehling
  • G. Schwarz
  • P. Legendre
  • J.C. Meier

Journal

  • European Journal of Neuroscience

Quellenangabe

  • Eur J Neurosci 30 (6): 1077-1091

Zusammenfassung

  • Glycine receptor (GlyR) alpha 3 is involved in vision, and processing of acoustic and nociceptive signals, and RNA editing of GLRA3 transcripts was associated with hippocampal pathophysiology of mesial temporal lobe epilepsy (TLE). However, neither the role of GlyR alpha 3 splicing in hippocampal neurons nor the expression of splice variants have yet been elucidated. We report here that the long (L) splice variant of GlyR alpha 3 predominates in the brain of rodents. Cellular analysis using primary hippocampal neurons and hippocampus cryosections revealed preferential association of synaptic alhpa 3L clusters with glutamatergic nerve endings in strata granulare and pyramidale. In primary hippocampal neurons GlyR alpha 3L clusters also preferred glutamatergic nerve endings while alpha 3K was mainly in a diffuse state. Co-expression of GlyR beta subunit with alpha 3L or alpha 3K produced heteromeric receptor clusters and favoured their association with GABAergic terminals. However, heteromeric alpha 3L was still more efficient than heteromeric alpha 3K in associating with glutamatergic nerve endings. To give physiological relevance to these results we have finally analysed GlyR alpha 3 splicing in human hippocampus obtained from patients with intractable TLE. As up-regulation of alpha 3K occurred at the expense of alpha 3L in TLE patients with a severe course of disease and a high degree of hippocampal damage, our results again involve post-transcriptional processing of GLRA3 transcripts in the pathophysiology of TLE.


DOI

doi:10.1111/j.1460-9568.2009.06903.x