Mentor: Joey Ransdell, Ph.D.

The axon initial segment (AIS) is a distinct region in neurons vital for initiating action potentials. This is due to the high concentration of voltage-gated potassium and sodium channels along with scaffolding proteins like Ankyrin G, which maintain structural integrity and are critical for the appropriate localization and distribution of ion channels at the AIS. Ion channel expression at the AIS affects the functionality and efficiency of neuronal action potential generation. Changes to the AIS can drastically change the excitability of neurons. Investigating the composition of the neuronal AIS across cell types can be used to better understand the mechanisms underlying disorders of the nervous system.

The AIS is frequently implicated in neurological diseases. AIS length and composition have all been linked to numerous neurological diseases such as Autism Spectrum disorder (ASD), epilepsy, cerebellar ataxias, and other conditions. Reduced expression levels of voltage gated sodium channels (Nav) at the AIS can reduce action potenial generation and increase action potenial threshold voltages; resulting in attenuated neuronal electrical signals.

In this project, we are working to investigate the AIS of cerebellar Purkinje neurons using both Cre-negative (-) and Cre-positive (+) transgenic mouse models. To identify and characterize AIS properties, we are using immunofluorescent labeing. Specifically, we are measuring the immunofluorescent signatures generated by voltage-gated sodium channel and ankyrin G expression at the Purkinje neuron AIS.

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