Spillover-mediated transmission at inhibitory synapses promoted by high affinity alpha6 subunit GABA(A) receptors and glomerular geometry.
Divergence and convergence of synaptic connections make a crucial contribution to the information processing capacity of the brain. Until recently, it was thought that transmitter released at a synapse affected only a specific postsynaptic cell. We show here that spillover of inhibitory transmitter at the Golgi to granule cell synapse produces significant cross-talk to non-postsynaptic cells, which is promoted both by the anatomical specialization of this glomerular synapse and by the presence of the high affinity alpha6 subunit-containing GABA(A) receptor in granule cells. Cross-talk is manifested as a novel slow rising and decaying small amplitude inhibitory postsynaptic current (IPSC) that can also contribute a long-lasting component to more typical IPSCs, which is prolonged by inhibition of the neuronal GABA transporter GAT-1. Because of the long duration of IPSCs generated by spillover, the total charge carried is three times that of IPSCs generated by directly connected terminals. GABA spillover within the mossy fiber glomerulus may play an important role in regulating the number of granule cells active in the cerebellar cortex, a regulation that is suggested by theoretical models to optimize cerebellar information processing.
Rossi
D J
DJ
Department of Physiology, University College London, United Kingdom.
Hamann
M
M
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D004558:Electric Stimulation; D050485:GABA Plasma Membrane Transport Proteins; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D026901:Membrane Transport Proteins; D008959:Models, Neurological; D009412:Nerve Fibers / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D027361:Organic Anion Transporters; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D011963:Receptors, GABA-A / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters; D011963:Receptors, GABA-A; C493415:Slc6a1 protein, rat; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid