Receptors and second messengers involved in long-term depression in rat cerebellar slices in vitro: a reappraisal.
In patch-clamped Purkinje cells (PCs), bath application of the ionotropic glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) prevents induction of long-term depression (LTD) of parallel fibre (PF)-mediated EPSPs by a pairing protocol between Ca2+ spike firing and PF stimulation whereas bath application of (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), a metabotropic glutamate (mGLU) receptor antagonist, does not. On the other hand, LTD can be also induced by pairing direct depolarization of PCs with activation of mGLU receptors by 1S,3R-aminocyclopentyl-dicarboxylate (1S,3R-ACPD), even in the presence of CNQX. In this case, LTD induction is not consistently blocked by bath application of the nitric oxide synthase inhibitor, NG-methyl-L-arginine (L-NMMA), whereas it is strongly blocked when the protein kinase C inhibitor peptide 19-36 is dialysed into PCs. These results are at variance with LTD induced by a pairing protocol between Ca2+ spikes and PF-mediated EPSPs which depends to the same extent on both cascades. Finally, thapsigargin, which depletes most intracellular Ca2+ pools, does not block induction of LTD by a pairing protocol between Ca2+ spikes and PF-mediated EPSPs whereas it prevents the induction of LTD depending on strong mGLU receptor activation.
Hémart
N
N
ERS CNRS F0100, Bâtiment 440, Université Paris-Sud, Orsay, France.
Daniel
H
H
Jaillard
D
D
Crépel
F
F
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002531:Cerebellum / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D015290:Second Messenger Systems; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D013729:Terpenes; D019284:Thapsigargin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000252:Calcium-Transporting ATPases; D002118:Calcium