Activation of presynaptic GABA(A) receptors induces glutamate release from parallel fiber synapses.
The parallel fibers relay information coming into the cerebellar cortex from the mossy fibers, and they form synapses with molecular layer interneurons (MLIs) and Purkinje cells. Here we show that activation of ionotropic GABA receptors (GABA(A)Rs) induces glutamate release from parallel fibers onto both MLIs and Purkinje cells. These GABA-induced EPSCs have kinetics and amplitudes identical to random spontaneous currents (sEPSCs), but, unlike sEPSCs, they occur in bursts of between one and five successive events. The variation in amplitude of events within bursts is significantly less than the variation of all sEPSC amplitudes, suggesting that the bursts result from repetitive activation of single presynaptic fibers. Electron microscopy of immunogold-labeled alpha-1 subunits revealed GABA(A)Rs on parallel fiber terminals. We suggest that the activation of these receptors underlies the increased amplitude of parallel fiber-evoked Purkinje cell EPSCs seen with application of exogenous GABA or after the release of GABA from local interneurons. These results occur only when molecular layer GABA(A)Rs are activated, and the effects are abolished when the receptors are blocked by the GABA(A)R antagonist gabazine (5 microM). From these data, we conclude that GABA(A)Rs located on parallel fibers depolarize parallel fiber terminals beyond the threshold for Na+ channel activation and thereby induce glutamate release onto MLIs and Purkinje cells.
Stell
Brandon M
BM
Laboratoire de Physiologie Cérébrale, Unité de Formation et de Recherche Biomédicale, Université Paris Descartes, 75006 Paris, France. brandon.stell@univ-paris5.fr
Rostaing
Philippe
P
Triller
Antoine
A
Marty
Alain
A
D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000166:cytology*; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D007395:Interneurons / Q000166:cytology; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009118:Muscimol / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010721:Phosphinic Acids / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D011412:Propanolamines / Q000494:pharmacology; D011689:Purkinje Cells / Q000166:cytology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D011963:Receptors, GABA-A; C085075:CGP 55845A; D009118:Muscimol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
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