039-22 – Subunit-specific mechanisms by which voltage-gated potassium channels contribute to synaptic plasticity and neuronal excitability in health and disease

Kv3 voltage-gated potassium currents rapidly repolarize action potentials and underlie fast-spiking neuronal phenotypes, enabling high frequency firing with temporal precision. These channels are expressed throughout the brain; here we focus on the auditory brainstem, where Kv3s are responsible for precise temporal integration of signals from both ears to ensure correct sound-source localization. We use the giant synapse of the auditory brainstem, the Calyx of Held, as a model for synaptic plasticity to understand how different Kv3 channel subunits contribute to neurotransmitter release and transmission both in health and disease.
A single point mutation in the gene for Kv3.3 subunit results in a rare genetic neurodegenerative disorder, Spinocerebellar Ataxia type 13 (SCA13), characterized by motor deficits, cerebellar atrophy and impairments in sound localization abilities.
By employing whole-cell patch clamp electrophysiology and pharmacology, the main focus of this research is to investigate the effects of such mutation on a CRISPR/Cas9 gene-edited mouse model for SCA13, in order to understand the molecular basis of the pathophysiology of the condition.