Retrograde activation of presynaptic NMDA receptors enhances GABA release at cerebellar interneuron-Purkinje cell synapses.
Synaptic inhibition is a vital component in the control of cell excitability within the brain. Here we report a newly identified form of inhibitory synaptic plasticity, termed depolarization-induced potentiation of inhibition, in rodents. This mechanism strongly potentiated synaptic transmission from interneurons to Purkinje cells after the termination of depolarization-induced suppression of inhibition. It was triggered by an elevation of Ca(2+) in Purkinje cells and the subsequent retrograde activation of presynaptic NMDA receptors. These glutamate receptors promoted the spontaneous release of Ca(2+) from presynaptic ryanodine-sensitive Ca(2+) stores. Thus, NMDA receptor-mediated facilitation of transmission at this synapse provides a regulatory mechanism that can dynamically alter the synaptic efficacy at inhibitory synapses.
Duguid
Ian C
IC
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Smart
Trevor G
TG
D000818:Animals; D000831:Animals, Newborn; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology*; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000528:radiation effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D000077285:Rimonabant; D012433:Ryanodine / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D007527:Isoenzymes; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; D010880:Piperidines; D011720:Pyrazoles; D016194:Receptors, N-Methyl-D-Aspartate; D026941:Sodium Channel Blockers; D016708:Synaptophysin; D002104:Cadmium; D012433:Ryanodine; D013779:Tetrodotoxin; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000077285:Rimonabant; D002118:Calcium