Altered Purkinje cell pacemaking underlies motor deficits in mouse models of cerebellar ataxia

Purkinje cells are key regulators of motor coordination, and disruptions in their regular firing patterns contribute to cerebellar ataxias. This thesis examines how altered Purkinje cell pacemaking affects motor control in two mouse models. In a model of episodic ataxia type 1 (EA1), stress‑related β‑adrenergic signaling worsened imprecise firing, while acetazolamide restored precision and blocked stress effects, suggesting a cellular basis for EA1 attacks. In a second model with reduced SK2 channel expression, widespread irregular firing impaired balance only when the remaining normally firing lobules were ablated. These findings highlight the role of precise Purkinje cell output in motor coordination.