Na(v)1.6a is required for normal activation of motor circuits normally excited by tactile stimulation.

Published

Journal Article

A screen for zebrafish motor mutants identified two noncomplementing alleles of a recessive mutation that were named non-active (nav(mi89) and nav(mi130)). nav embryos displayed diminished spontaneous and touch-evoked escape behaviors during the first 3 days of development. Genetic mapping identified the gene encoding Na(V)1.6a (scn8aa) as a potential candidate for nav. Subsequent cloning of scn8aa from the two alleles of nav uncovered two missense mutations in Na(V)1.6a 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 voltage-dependent 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 Na(V)1.6a was required for touch-induced activation of the swim locomotor network.

Full Text

Cited Authors

  • Low, SE; Zhou, W; Choong, I; Saint-Amant, L; Sprague, SM; Hirata, H; Cui, WW; Hume, RI; Kuwada, JY

Published Date

  • June 2010

Published In

Volume / Issue

  • 70 / 7

Start / End Page

  • 508 - 522

PubMed ID

  • 20225246

Pubmed Central ID

  • 20225246

Electronic International Standard Serial Number (EISSN)

  • 1932-846X

International Standard Serial Number (ISSN)

  • 1932-8451

Digital Object Identifier (DOI)

  • 10.1002/dneu.20791

Language

  • eng