Topic: SCA13

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 cerebell

Aims: SCA13 patients carrying the R420H mutation in Kv3.3 also have compromised sound localization based on inferior processing of interaural differences in time and intensity of sound. These patients show no pure-tone deficit in the audiogram and their peripheral auditory system seems unaffected. The Kv3.3 subunit of voltage-gated potassium channels is highly expressed in fast-firing neurons of the auditory pathway, including the medial nucleus of the trapezoid body (MNTB) and the lateral superior olive (LSO) and is often co-expressed with the Kv3.1 subunit. Here, we investigate how this Kv3.

Aims: SCA13 patients exhibit an extracerebellar auditory phenotype characterized by sound localization deficits, despite normal audiograms. This phenotype is caused by the R420H point mutation in the KCNC3 gene which encodes for Kv3.3 subunits of high-voltage gated potassium channels. Here, we investigate how this mutation leads to disruption of temporal processing along the auditory pathway.Methods: The R420H mouse model was created using CRISPR-Cas9. Whole-cell patch-clamp electrophysiology and afferent synaptic stimulation in acute mouse brain slices were used to characterize neural firing