title: Adaptive regulation maintains posttetanic potentiation at cerebellar granule cell synapses in the absence of calcium-dependent PKC.
abstract: Posttetanic potentiation (PTP) is a transient, calcium-dependent increase in the efficacy of synaptic transmission following elevated presynaptic activity. The calcium-dependent protein kinase C (PKC(Ca)) isoforms PKCα and PKCβ mediate PTP at the calyx of Held synapse, with PKCβ contributing significantly more than PKCα. It is not known whether PKC(Ca) isoforms play a conserved role in PTP at other synapses. We examined this question at the parallel fiber → Purkinje cell (PF→PC) synapse, where PKC inhibitors suppress PTP. We found that PTP is preserved when single PKC(Ca) isoforms are knocked out and in PKCα/β double knock-out (dko) mice, even though in the latter all PKC(Ca) isoforms are eliminated from granule cells. However, in contrast to wild-type and single knock-out animals, PTP in PKCα/β dko animals is not suppressed by PKC inhibitors. These results indicate that PKC(Ca) isoforms mediate PTP at the PF→PC synapse in wild-type and single knock-out animals. However, unlike the calyx of Held, at the PF→PC synapse either PKCα or PKCβ alone is sufficient to mediate PTP, and if both isoforms are eliminated a compensatory PKC-independent mechanism preserves the plasticity. These results suggest that a feedback mechanism allows granule cells to maintain the normal properties of short-term synaptic plasticity even when the mechanism that mediates PTP in wild-type mice is eliminated.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Diasynou
authors.initials: D
authors.lastname: Fioravante
authors.forename: Michael H
authors.initials: MH
authors.lastname: Myoga
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Wade G
authors.initials: WG
authors.lastname: Regehr
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology*; D005260:Female; D018682:GABA Agents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000172:deficiency / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000172:deficiency / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018682:GABA Agents; D010880:Piperidines; D011720:Pyrazoles; C103505:AM 251; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D002118:Calcium