Na _V 1.1 is the primary voltage-gated Na ⁺ channel in several classes of GABAergic interneurons, and its reduced activity leads to reduced excitability and decreased GABAergic tone. Here, we show that Na _V 1.1 channels are expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus. Mice carrying a heterozygous loss of function mutation in the Scn1a gene ( Scn1a ^+/− ), which encodes the pore-forming α-subunit of the Na _V 1.1 channel, have longer circadian period than WT mice and lack light-induced phase shifts. In contrast, Scn1a ^+/− mice have exaggerated light-induced negative-masking behavior and normal electroretinogram, suggesting an intact retina light response. Scn1a ^+/− mice show normal light induction of c-Fos and mPer1 mRNA in ventral SCN but impaired gene expression responses in dorsal SCN. Electrical stimulation of the optic chiasm elicits reduced calcium transients and impaired ventro-dorsal communication in SCN neurons from Scn1a ^+/− mice, and this communication is barely detectable in the homozygous gene KO ( Scn1a ^−/− ). Enhancement of GABAergic transmission with tiagabine plus clonazepam partially rescues the effects of deletion of Na _V 1.1 on circadian period and phase shifting. Our report demonstrates that a specific voltage-gated Na ⁺ channel and its associated impairment of SCN interneuronal communication lead to major deficits in the function of the master circadian pacemaker. Heterozygous loss of Na _V 1.1 channels is the underlying cause for severe myoclonic epilepsy of infancy; the circadian deficits that we report may contribute to sleep disorders in severe myoclonic epilepsy of infancy patients.

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