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Na V 1.6a is required for normal activation of motor circuits normally excited by tactile stimulation
Author(s) -
Low Sean E.,
Zhou Weibin,
Choong Ingxin,
SaintAmant Louis,
Sprague Shawn M.,
Hirata Hiromi,
Cui Wilson W.,
Hume Richard I.,
Kuwada John Y.
Publication year - 2010
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.20791
Subject(s) - biology , mutant , zebrafish , neuroscience , stimulation , genetic screen , electrophysiology , premovement neuronal activity , gene , microbiology and biotechnology , genetics
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. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:508–522, 2010