Potentiation of Mossy Fiber EPSCs in the Cerebellar Nuclei by NMDA Receptor Activation followed by Postinhibitory Rebound Current

Jason R. Pugh, Indira M. Raman

Research output: Contribution to journalArticle

173 Scopus citations

Abstract

Behavioral and computational studies predict that synaptic plasticity of excitatory mossy fiber inputs to cerebellar nuclear neurons is required for associative learning, but standard tetanization protocols fail to potentiate nuclear cell EPSCs in mouse cerebellar slices. Nuclear neurons fire action potentials spontaneously unless strongly inhibited by Purkinje neurons, raising the possibility that plasticity-triggering signals in these cells differ from those at classical Hebbian synapses. Based on predictions of neuronal activity during delay eyelid conditioning, we developed quasi-physiological induction protocols consisting of high-frequency mossy fiber stimulation and postsynaptic hyperpolarization. Robust, NMDA receptor-dependent potentiation of nuclear cell EPSCs occurred with protocols including a 150-250 ms hyperpolarization in which mossy fiber stimulation preceded a postinhibitory rebound depolarization. Mossy fiber stimulation potentiated EPSCs even when postsynaptic spiking was prevented by voltage-clamp, as long as rebound current was evoked. These data suggest that Purkinje cell inhibition guides the strengthening of excitatory synapses in the cerebellar nuclei.

Original languageEnglish (US)
Pages (from-to)113-123
Number of pages11
JournalNeuron
Volume51
Issue number1
DOIs
StatePublished - Jul 6 2006
Externally publishedYes

Keywords

  • MOLNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

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