Abstract : Long-term potentiation (LTP) of mossy fiber EPSCs in the cerebellar nuclei is controlled by synapti
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Abstract : Long-term potentiation (LTP) of mossy fiber EPSCs in the cerebellar nuclei is controlled by synaptic inhibition from Purkinje neurons. EPSCs are potentiated by a sequence of excitation inhibition and disinhibition raising the question of how these stimuli interact to induce plasticity. Here we find that synaptic excitation inhibition and disinhibition couple to different calcium-dependent signaling pathways. In LTP induction protocols constitutively active calcineurin can replace synaptic excitation and constitutively active alpha-CaMKII can replace calcium influx associated with resumption of spiking upon disinhibition. Additionally nimodipine can replace hyperpolarization indicating that inhibition of firing decreases Ca influx through L-type Ca channels providing a necessary signal for LTP. Together these data suggest that potentiation develops after a calcineurin priming signal combines with an alpha-CaMKII triggering signal if and only if L-type Ca current is reduced. Thus hyperpolarization induced by synaptic inhibition actively controls excitatory synaptic plasticity in the cerebellar nuclei.Copyright 2010 Elsevier Inc. All rights reserved.PMID 20510859 PubMed - indexed for MEDLINEPMCID PMC2886803 Available on 2011/5/27Publication Types MeSH Terms Substances Grant SupportPublication Types Comparative StudyResearch Support N.I.H. ExtramuralMeSH TermsAnimalsCalcium Channel Blockers/pharmacologyCalcium Channels L-Type/metabolism*Calcium Channels L-Type/physiologyCerebellar Nuclei/drug effectsCerebellar Nuclei/physiology*Excitatory Postsynaptic Potentials/drug effectsExcitatory Postsynaptic Potentials/physiology*HumansLong-Term Potentiation/drug effectsLong-Term Potentiation/physiology*MiceMice Inbred C57BLNeural Inhibition/drug effectsNeural Inhibition/physiology*Synapses/drug effectsSynapses/physiology*SubstancesCalcium Channel BlockersCalcium Channels L-TypeGrant SupportF32 NS067831/NS/NINDS NIH HHS/United StatesNS39395/NS/NINDS NIH HHS/United StatesT32 NS041234/NS/NINDS NIH HHS/United StatesT32 NS041234-09/NS/NINDS NIH HHS/United StatesLinkOut - more resourcesFull Text SourcesElsevier ScienceEBSCOOhioLINK Electronic Journal CenterSwets Information ServicesOther Literature SourcesCOS Scholar Universe Supplemental Content Related citations Mechanisms of potentiation of mossy fiber EPSCs in the cerebellar nuclei by coincident synaptic excitation and inhibition. J Neurosci. 2008 Mechanisms of potentiation of mossy fiber EPSCs in the cerebellar nuclei by coincident synaptic excitation and inhibition.Pugh JR Raman IM. J Neurosci. 2008 Oct 15 28(42)10549-60. Ca currents activated by spontaneous firing and synaptic disinhibition in neurons of the cerebellar nuclei. J Neurosci. 2009 Ca currents activated by spontaneous firing and synaptic disinhibition in neurons of the cerebellar nuclei.Zheng N Raman IM. J Neurosci. 2009 Aug 5 29(31)9826-38. Potentiation of mossy fiber EPSCs in the cerebellar nuclei by NMDA receptor activation followed by postinhibitory rebound current. Neuron. 2006 Potentiation of mossy fiber EPSCs in the cerebellar nuclei by NMDA receptor activation followed by postinhibitory rebound current.Pugh JR Raman IM. Neuron. 2006 Jul 6 51(1)113-23. Review Synaptic inhibition excitation and plasticity in neurons of the cerebellar nuclei. Cerebellum. 2010 Review Synaptic inhibition excitation and plasticity in neurons of the cerebellar nuclei.Zheng N Raman IM. Cerebellum. 2010 Mar 9(1)56-66. Review Hippocampal long-term synaptic plasticity and signal amplification of NMDA receptors. Crit Rev Neurobiol. 2006 Review Hippocampal long-term synaptic plasticity and signal amplification of NMDA receptors.MacDonald JF Jackson MF Beazely MA. Crit Rev Neurobiol. 2006 18(1-2)71-84. See reviews... See all... Recent activity Clear Turn Off Turn On Deactivation of L-type Ca current by inhibition controls LTP at excitatory synap... Deactivation of L-type Ca current by inhibition controls LTP at excitatory synapses in the cerebellar nuclei.Neuron. 2010 May 27 66(4)550-9. PubMed Your browsing activity is empty. Activity recording is turned off. Turn recording back on See more... 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