Document Detail

Synaptic homeostasis in a zebrafish glial glycine transporter mutant.
MedLine Citation:
PMID:  18715895     Owner:  NLM     Status:  MEDLINE    
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.
Rebecca Mongeon; Michelle R Gleason; Mark A Masino; Joseph R Fetcho; Gail Mandel; Paul Brehm; Julia E Dallman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-08-20
Journal Detail:
Title:  Journal of neurophysiology     Volume:  100     ISSN:  0022-3077     ISO Abbreviation:  J. Neurophysiol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-13     Completed Date:  2008-12-05     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  0375404     Medline TA:  J Neurophysiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1716-23     Citation Subset:  IM    
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MeSH Terms
Axons / physiology
Behavior, Animal / physiology
Escape Reaction / physiology
Excitatory Postsynaptic Potentials / physiology
Glycine / metabolism
Glycine Plasma Membrane Transport Proteins / genetics*,  physiology*
Homeostasis / physiology*
Motor Neurons / physiology
Muscle, Skeletal / metabolism,  physiology
Neuroglia / metabolism*
Patch-Clamp Techniques
Receptors, Glycine / biosynthesis
Synapses / physiology*
Synaptic Potentials / physiology
Zebrafish / genetics*,  physiology*
Zebrafish Proteins / genetics*,  physiology*
Grant Support
NS-048200/NS/NINDS NIH HHS; NS-18205/NS/NINDS NIH HHS; NS-25639/NS/NINDS NIH HHS; NS-44758/NS/NINDS NIH HHS; R01 NS026539/NS/NINDS NIH HHS; R01 NS026539-25/NS/NINDS NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Glycine Plasma Membrane Transport Proteins; 0/Receptors, Glycine; 0/SLC6A9 protein, zebrafish; 0/Zebrafish Proteins; TE7660XO1C/Glycine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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