Prolonged postinhibitory rebound firing in the cerebellar nuclei mediated by group I metabotropic glutamate receptor potentiation of l-type calcium currents

Nan Zheng, Indira M. Raman

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Neurons in the cerebellar nuclei fire at accelerated rates for prolonged periods after trains of synaptic inhibition that interrupt spontaneous firing. Both in vitro and in vivo, however, this prolonged rebound firing is favored by strong stimulation of afferents, suggesting that neurotransmitters other than GABA may contribute to the increased firing rates. Here, we tested whether metabotropic glutamate receptors modulate excitability of nuclear cells in cerebellar slices from mouse. In current clamp, the prolonged rebound firing rate after high-frequency synaptic stimulation was reduced by a variety of group I mGluR antagonists, including CPCCOEt [7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester], JNJ16259685 (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)- (cis-4-methoxycyclohexyl)-methanone) plus MPEP, or 3-MATIDA (_-amino-5-carboxy-3-methyl-2-thiopheneacetic acid) plus MPEP, as long as both mGluR1 and mGluR5 were blocked. This mGluR-dependent acceleration of firing w as reduced but still evident when IPSPs were prevented by GABAA receptor antagonists. In voltage clamp, voltage ramps revealed a non-inactivating, low-voltage-activated, nimodipinesensitive current that was enhanced by the selective group I mGluR agonist s-DHPG [(S)-3,5- ihydroxyphenylglycine]. This putative L-type current also increased when mGluRs were activated by trains of evoked synaptic currents instead of direct application of agonist. In current clamp, blocking L-type Ca channels with the specific blocker nifedipine greatly reduced prolonged poststimulus firing and occluded the effect of adding group I mGluR antagonists. Thus, potentiation of a low-voltage-activated L-type current by synaptically released glutamate accounted nearly fully for the mGluR-dependent acceleration of firing. Together, these data suggest that prolonged rebound firing in the cerebellar nuclei in vivo is most likely to occur when GABAA and mGluRs are simultaneously activated by concurrent excitation and inhibition.

Original languageEnglish (US)
Pages (from-to)10283-10292
Number of pages10
JournalJournal of Neuroscience
Volume31
Issue number28
DOIs
StatePublished - Jul 13 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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