Synaptic homeostasis in a zebrafish glial glycine transporter mutant

Rebecca Mongeon, Michelle R. Gleason, Mark A. Masino, Joseph R. Fetcho, Gail Mandel, Paul Brehm, Julia E. Dallman

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Truncated escape responses characteristic of the zebrafish shocked mutant result from a defective glial glycine transporter (GlyT1). In homozygous GlyT1 mutants, irrigating brain ventricles with glycine-free solution rescues normal swimming. Conversely, elevating brain glycine levels restores motility defects. These experiments are consistent with previous studies that demonstrate regulation of global glycine levels in the CNS as a primary function of GlyT1. As GlyT1 mutants mature, their ability to mount an escape response naturally recovers. To understand the basis of this recovery, we assay synaptic transmission in primary spinal motor neurons by measuring stimulus-evoked postsynaptic potentials. At the peak of the motility defect, inhibitory synaptic potentials are both significantly larger and more prolonged indicating a prominent role for GlyT1 in shaping fast synaptic transmission. However, as GlyT1 mutants naturally regain their ability to swim, the amplitude of inhibitory potentials decreases to below wild-type levels. In parallel with diminishing synaptic potentials, the glycine concentration required to evoke the mutant motility defect increases 61-fold during behavioral recovery. Behavioral recovery is also mirrored by a reduction in the levels of both glycine receptor protein and transcript. These results suggest that increased CNS glycine tolerance and reduced glycine receptor expression in GlyT1 mutants reflect compensatory mechanisms for functional recovery from excess nervous system inhibition.

Original languageEnglish (US)
Pages (from-to)1716-1723
Number of pages8
JournalJournal of neurophysiology
Volume100
Issue number4
DOIs
StatePublished - Oct 1 2008

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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    Mongeon, R., Gleason, M. R., Masino, M. A., Fetcho, J. R., Mandel, G., Brehm, P., & Dallman, J. E. (2008). Synaptic homeostasis in a zebrafish glial glycine transporter mutant. Journal of neurophysiology, 100(4), 1716-1723. https://doi.org/10.1152/jn.90596.2008