Dr. Kay Redfield Jamison, a psychiatry professor who has bipolar disorder (also known as manic-depression) provides strong evidence for a link between creativity and bipolar illness (1993). Bipolar individuals may naturally use creativity to understand and heal themselves through art; however, this mysterious link between bipolar disorder and creativity is not yet explained by psychiatrists (Mondimore, 2014). Spaniol also suggests a link between art and mental illness, indicating that art can be used for insight and emotional growth (2001).

We thank Dr. Jacopo Magistretti for invaluable discussion and for sharing research data prior to publication. We further thank Christy Pardee, Stacey Rubin, and Pasqualina Farisello for their technical assistance. This research was funded by PHS grant R01-NS39906 (M.G), CUNY equipment grant (M.G.), and EU-SENSOPAC and CARIPLO grants (E.D.'A.).

Supported by US National Institutes of Health (NIH) grants NS35806 and NS34179. C.I. is the recipient of a Javits award from NIH/National Institute of Neurological Disorders and Stroke. We thank B.H. Koller and S.L. Tilley for providing the Ep1-/- mice, L. Qian for studies in hippocampal slice cultures, C. Gooden for tissue cultures studies and C. Pardee for assistance with histology.

Neurons integrate and encode complex synaptic inputs into action potential outputs through a process termed ''intrinsic excitability.'' Here, we report the essential contribution of fibroblast growth factor homologous factors (FHFs), a family of voltage-gated sodium channel binding proteins, to this process. Fhf1 À/À Fhf4 À/À mice suffer from severe ataxia and other neurological deficits. In mouse cerebellar slice recordings, WT granule neurons can be induced to fire action potentials repetitively ($60 Hz), whereas Fhf1 À/À Fhf4 À/À neurons often fire only once and at an elevated voltage spike threshold. Sodium channels in Fhf1 À/À Fhf4 À/À granule neurons inactivate at more negative membrane potential, inactivate more rapidly, and are slower to recover from the inactivated state. Altered sodium channel physiology is sufficient to explain excitation deficits, as tested in a granule cell computer model. These findings offer a physiological mechanism underlying human spinocerebellar ataxia induced by Fhf4 mutation and suggest a broad role for FHFs in the control of excitability throughout the CNS.