Graded coexpression of ion channel, neurofilament, and synaptic genes in fast-spiking vestibular nucleus neurons

Takashi Kodama, Aryn H. Gittis, Minyoung Shin, Keith Kelleher, Kristine E. Kolkman, Lauren McElvain, Minh Lam, Sascha Du Lac

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Computations that require speed and temporal precision are implemented throughout the nervous system by neurons capable of firing at very high rates, rapidly encoding and transmitting a rich amount of information, but with substantial metabolic and physical costs. For economical fast spiking and high throughput information processing, neurons need to optimize multiple biophysical properties in parallel, but the mechanisms of this coordination remain unknown.Wehypothesized that coordinated gene expression may underlie the coordinated tuning of the biophysical properties required for rapid firing and signal transmission. Taking advantage of the diversity of fast-spiking cell types in the medial vestibular nucleus of mice of both sexes, we examined the relationship between gene expression, ionic currents, and neuronal firing capacity. Across excitatory and inhibitory cell types, genes encoding voltage-gated ion channels responsible for depolarizing and repolarizing the action potential were tightly coexpressed, and their absolute expression levels increased with maximal firing rate. Remarkably, this coordinated gene expression extended to neurofilaments and specific presynaptic molecules, providing a mechanism for coregulating axon caliber and transmitter release to match firing capacity. These findings suggest the presence of a module of genes, which is coexpressed in a graded manner and jointly tunes multiple biophysical properties for economical differentiation of firing capacity. The graded tuning of fast-spiking capacity by the absolute expression levels of specific ion channels provides a counterexample to the widely held assumption that cell-type-specific firing patterns can be achieved via a vast combination of different ion channels.

Original languageEnglish (US)
Pages (from-to)496-508
Number of pages13
JournalJournal of Neuroscience
Issue number3
StatePublished - Jan 15 2020


  • Flocculus
  • High-frequency firing
  • Ion channel genes
  • Kv3
  • Pre-cerebellar
  • Sodium channel

ASJC Scopus subject areas

  • Neuroscience(all)


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