Rhythmicity without synchrony in the electrically uncoupled inferior olive

Michael A. Long, Michael R. Deans, David L. Paul, Barry W. Connors

Research output: Contribution to journalArticlepeer-review

182 Scopus citations


Neurons of the inferior olivary nucleus (IO) form the climbing fibers that excite Purkinje cells of the cerebellar cortex. IO neurons are electrically coupled through gap junctions, and they generate synchronous, subthreshold oscillations of membrane potential at ∼5-10 Hz. Experimental and theoretical studies have suggested that both the rhythmicity and synchrony of IO neurons require electrical coupling. We recorded from pairs of IO neurons in slices of mouse brainstem in vitro. Most pairs of neurons from wild-type (WT) mice were electrically coupled, but coupling was rare and weak between neurons of knock-out (KO) mice for connexin36, a neuronal gap junction protein. IO cells in both WT and KO mice generated rhythmic membrane fluctuations of similar frequency and amplitude. Oscillations in neighboring pairs of WT neurons were strongly synchronized, whereas the oscillations of KO pairs were uncorrelated. Spontaneous oscillations in KO neurons were not blocked by tetrodotoxin. Spontaneously oscillating neurons of both WT and KO mice generated occasional action potentials in phase with their membrane rhythms, but only the action potentials of WT neuron pairs were synchronous. Harmaline, a β-carboline derivative thought to induce tremor by facilitating rhythmogenesis in the IO, was injected systemically into WT and KO mice. Harmaline-induced tremors were robust and indistinguishable in the two genotypes, suggesting that gap junction-mediated synchrony does not play a role in harmaline-induced tremor. We conclude that electrical coupling is not necessary for the generation of spontaneous subthreshold oscillations in single IO neurons, but that coupling can serve to synchronize rhythmic activity among IO neurons.

Original languageEnglish (US)
Pages (from-to)10898-10905
Number of pages8
JournalJournal of Neuroscience
Issue number24
StatePublished - Dec 15 2002
Externally publishedYes


  • Connexin36
  • Electrical coupling
  • Gap junction
  • Harmaline
  • Inferior olive
  • Rhythms
  • Synchrony

ASJC Scopus subject areas

  • Neuroscience(all)


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