NaV1.6a is required for normal activation of motor circuits normally excited by tactile stimulation

Sean E. Low, Weibin Zhou, Ingxin Choong, Louis Saint-Amant, Shawn M. Sprague, Hiromi Hirata, Wilson W. Cui, Richard I. Hume, John Y. Kuwada

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


A screen for zebrafish motor mutants identified two noncomplementing alleles of a recessive mutation that were named non-active (navmi89 and navmi130). nav embryos displayed diminished spontaneous and touch-evoked escape behaviors during the first 3 days of development. Genetic mapping identified the gene encoding NaV1.6a (scn8aa) as a potential candidate for nav. Subsequent cloning of scn8aa from the two alleles of nav uncovered two missense mutations in NaV1.6a that eliminated channel activity when assayed heterologously. Furthermore, the injection of RNA encoding wild-type scn8aa rescued the nav mutant phenotype indicating that scn8aa was the causative gene of nav. In-vivo electrophysiological analysis of the touch-evoked escape circuit indicated that voltagedependent inward current was decreased in mechanosensory neurons in mutants, but they were able to fire action potentials. Furthermore, tactile stimulation of mutants activated some neurons downstream of mechanosensory neurons but failed to activate the swim locomotor circuit in accord with the behavioral response of initial escape contractions but no swimming. Thus, mutant mechanosensory neurons appeared to respond to tactile stimulation but failed to initiate swimming. Interestingly fictive swimming could be initiated pharmacologically suggesting that a swim circuit was present in mutants. These results suggested that NaV1.6a was required for touch-induced activation of the swim locomotor network.

Original languageEnglish
Pages (from-to)508-522
Number of pages15
JournalDevelopmental Neurobiology
Issue number7
StatePublished - Jun 2010
Externally publishedYes


  • Motor behaviors
  • Zebrafish
  • scn8a


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