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Download CaV3.1 is tremor rhythm pacemaker
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CaV3.1 is tremor rhythm pacemaker Tremor is a rhythmic muscular contraction that has been implicated in physiological and pathological functions of brain; however, the molecular target underlying tremor rhythm synchronous 4-10Hz remains obscure. Here, we demonstrate that rhythmic oscillations, which arose from the inferior olive and then propagated to cerebellar motor circuits, was inducible in wild-type mice but not in mice lacking the CaV3.1 gene in a pharmacological model of essential tremor induced by harmaline. The CaV3.1-deficient inferior olive neurons lacked subthreshold membrane potential oscillations and failed to trigger 4-10 Hz rhythmic burst discharges in response to harmaline-induced hyperpolarization. In addition, selective knock-down of this gene in the inferior olive efficiently suppressed harmaline-induced tremor in wild-type mice; Thus, CaV3.1 is a molecular pacemaker substrate for the intrinsic neuronal oscillations in the inferior olive and is responsible for the rhythmic activation of motor circuits supporting motor coordination timing, and serves as the basis for essential tremor.
