Synaptic homeostasis in a zebrafish glial glycine transporter mutant.
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.
Mongeon
Rebecca
R
Howard Hughes Medical Institute, Department of Neurobiology and Behavior, State University of New York, Stony Brook, NY, USA.
Gleason
Michelle R
MR
Masino
Mark A
MA
Fetcho
Joseph R
JR
Mandel
Gail
G
Brehm
Paul
P
Dallman
Julia E
JE
D000483:Alleles; D000818:Animals; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D004597:Electroshock; D004924:Escape Reaction / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005998:Glycine / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D009457:Neuroglia / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D018009:Receptors, Glycine / Q000096:biosynthesis; D013569:Synapses / Q000502:physiology*; D055366:Synaptic Potentials / Q000502:physiology; D015027:Zebrafish / Q000235:genetics* / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology*
D050487:Glycine Plasma Membrane Transport Proteins; D018009:Receptors, Glycine; C507809:SLC6A9 protein, zebrafish; D029961:Zebrafish Proteins; D005998:Glycine