Aims: SCA13 is a hereditary disease caused by an autosomal-dominant mutation in the KCNC3 gene which encodes the Kv3.3 potassium channel subunit of high-voltage gated potassium channels. In humans, SCA13 leads to late onset ataxia, cerebellar atrophy, and the R420H mutation also causes sound localization deficits. Kv3.3 is abundantly expressed in the cerebellum where it promotes fast repolarization of action potentials and enables Purkinje neurons (PN) to fire bursts of spikes at very high rates. Here, we compared differential degrees of PN degeneration in the flocculus and the medial cerebellum.Methods: A R420H mouse model was created using CRISPR-Cas9. Ataxia was quantified through baseline activity on a force platform. Neural firing properties were measured using patch-clamp recording from cerebellar and floccular PNs. Degrees of degeneration were assessed by counting cell number, cell size, p62/cleaved caspase expression and subcellular distribution of Kv3.3.Results: Apoptotic cascades and electrophysiological deficits of PNs have been compared between wild type, heterozygote and homozygote mice aged 1-6 month. In homozygote mice, baseline tremor was increased, action potentials were significantly longer in duration, disrupting complex and simple spike patterns. Histological assessment revealed a near complete loss of PNs in the medial cerebellum, while floccular PNs largely survive.Conclusions: The R420H mutation disrupts action potential waveforms of simple as well as complex spikes, emphasizing the severity of the mutation as PNs form the sole output of the cerebellum. The survival of floccular PNs raises the question of possible differences in their connectivity and function.