Abstracts

Summary: Information processing in neurons relies on the integration of excitatory and inhibitory inputs to encode action potential (AP) firing. In most neurons the program that determines AP firing resides within the axon initial segment (AIS), a specialized domain of the axon proximal to the soma. The AIS has been increasingly in the spotlight as studies unravel the molecular basis of its functional and cell biological complexity, from AP initiation to disease and excitability dependent structural plasticity. The primary goal of this workshop is to highlight the role of the AIS in epileptogenesis. AIS function is dependent on clustering of a multitude of different ion channels, an intriguing number of which have been associated with human genetic epilepsy. Furthermore, recent evidence of activity dependent structural plasticity potentially implicates the AIS more generally in the pathology of epilepsy. Prof Rasband will start the session with an overview of the molecular anatomy of the AIS and discuss ideas and data on AIS-specific pathogenic mechanisms in neuronal injury. Prof Cooper will present functional studies on the vital role of potassium channels in the AIS in health and disease and Dr Wimmer will provide direct evidence for AIS-based pathogenic mechanisms in genetic epilepsy. Together, these three presentations will provide an overview of recent advances in the understanding of AIS dysfunction in neuronal pathogenesis. A secondary goal of the workshop is to stimulate discussion of future research on the role of AIS in epilepsy and its potential as a therapeutic target.