IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells.
In the rat cerebellum, Golgi cells receive serotonin-evoked inputs from Lugaro cells (L-IPSCs), in addition to spontaneous inhibitory inputs (S-IPSCs). In the present study, we analyze the pharmacology of these IPSCs and show that S-IPSCs are purely GABAergic events occurring at basket and stellate cell synapses, whereas L-IPSCs are mediated by GABA and glycine. Corelease of the two transmitters at Lugaro cell synapses is suggested by the fact that both GABA(A) and glycine receptors open during individual L-IPSCs. Double immunocytochemical stainings demonstrate that GABAergic and glycinergic markers are coexpressed in Lugaro cell axonal varicosities, together with the mixed vesicular inhibitory amino acid transporter. Lugaro cell varicosities are found apposed to glycine receptor (GlyR) clusters that are localized on Golgi cell dendrites and participate in postsynaptic complexes containing GABA(A) receptors (GABA(A)Rs) and the anchoring protein gephyrin. GABA(A)R and GlyR/gephyrin appear to form segregated clusters within individual postsynaptic loci. Basket and stellate cell varicosities do not face GlyR clusters. For the first time the characteristics of GABA and glycine cotransmission are compared with those of GABAergic transmission at identified inhibitory synapses converging onto the same postsynaptic neuron. The ratio of the decay times of L-IPSCs and of S-IPSCs is a constant value among Golgi cells. This indicates that, despite a high cell-to-cell variability of the overall IPSC decay kinetics, postsynaptic Golgi cells coregulate the kinetics of their two main inhibitory inputs. The glycinergic component of L-IPSCs is responsible for their slower decay, suggesting that glycinergic transmission plays a role in tuning the IPSC kinetics in neuronal networks.
Dumoulin
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Laboratoire de Biologie Cellulaire de la Synapse, Institut National de la Santé et de la Recherche Médicale U497, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8544, Ecole Normale Supérieure, 75005 Paris, France.
Triller
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Dieudonné
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D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D033921:Vesicular Transport Proteins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D050487:Glycine Plasma Membrane Transport Proteins; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; C118623:Slc32a1 protein, rat; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D033921:Vesicular Transport Proteins; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D013331:Strychnine; D005998:Glycine