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Genes Brain Behav. 2008 Aug;7(6):629-38. doi: 10.1111/j.1601-183X.2008.00399.x. Epub 2008 Mar 21.

Exaggerated emotional behavior in mice heterozygous null for the sodium channel Scn8a (Nav1.6).

Author information

1
Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109-2200, USA.

Abstract

The Scn8a gene encodes the alpha-subunit of Na(v)1.6, a neuronal voltage-gated sodium channel. Mice homozygous for mutations in the Scn8a gene exhibit motor impairments. Recently, we described a human family with a heterozygous protein truncation mutation in SCN8A. Rather than motor impairment, neuropsychological abnormalities were more common, suggesting a role for Scn8a in a more diverse range of behaviors. Here, we characterize mice heterozygous for a null mutation of Scn8a (Scn8a(+/-)mice) in a number of behavioral paradigms. We show that Scn8a(+/-)mice exhibit greater conditioned freezing in the Pavlovian fear conditioning paradigm but no apparent abnormalities in other learning and memory paradigms including the Morris water maze and conditioned taste avoidance paradigm. Furthermore, we find that Scn8a(+/-)mice exhibit more pronounced avoidance of well-lit, open environments as well as more stress-induced coping behavior. Together, these data suggest that Scn8a plays a critical role in emotional behavior in mice. Although the behavioral phenotype observed in the Scn8a(+/-)mice only partially models the abnormalities in the human family, we anticipate that the Scn8a(+/-)mice will serve as a valuable tool for understanding the biological basis of emotion and the human diseases in which abnormal emotional behavior is a primary component.

PMID:
18363861
PMCID:
PMC2879430
DOI:
10.1111/j.1601-183X.2008.00399.x
[Indexed for MEDLINE]
Free PMC Article

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