February 2004
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Journal of Clinical Investigation
Neurons so excited that they just can't hide itAtaxia is a lethal neurological disorder characterized by a lack of muscle coordination. The cerebellar cortex, the surface layer of the hindbrain, is often the target in ataxia and how a disruption in this region results in ataxia is of considerable interest. A report by K. George Chandy and colleagues from the University of California Irvine in the February 16 issue of the Journal of Clinical Investigation links ataxia to enhanced hyperexcitability of neurons in the deep cerebellar nuclei (DCN).
Within the cerebellum a class of output neurons known as Purkinje cells convey signals away from the cerebellum to the DCN. These cells also provide an inhibitory signal to DCN neurons, which ensures a normal firing rate and regular muscle coordination. Chandy and colleagues developed mice in which the small-conductance calcium-activated potassium (SK) channels � regulators of firing frequency � in the DCN were silenced. The authors found that these neurons had an increased firing rate and the mice were ataxic.
Importantly, the Purkinje cells input into the DCN remained intact and no other signs of degeneration in the cerebellar cortex or elsewhere in the brain were observed, indicating a direct relationship between DCN firing rate, regulation by SK channels, and proper muscle coordination. The report suggests that reestablishing a normal DCN firing rate might have therapeutic potential in the treatment of this debilitating disease.
TITLE: Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia
AUTHOR CONTACT:
K. George Chandy
University of California, Irvine, Irvine, California, USA.
Phone: (949) 824-6370
Fax: (949) 824-3143
E-mail: [email protected]
View the PDF of this article at: http://www.jci.org/cgi/content/full/113/4/582
ACCOMPANYING COMMENTARY: Into the depths of ataxia
AUTHOR CONTACT:
Harry T. Orr
Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA.
Phone: 612-625-3647
Fax: 612-626-7031
E-mail: [email protected]
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