A06 Regulation of inhibitory synaptic connections and distal neuronal complexity by the Ste20-like kinase SLK
The size and complexity of the dendritic arbor of a neuron play important roles in determining how synaptic inputs are converted to action potential output. Disruption of dendritic architecture is a major hallmark of so-called dysplastic neurons, which represent pathognomonic cellular elements of the most frequent and extremely epileptogenic focal lesions, focal cortical dysplasias type II (FCDII) and glioneuronal tumors, i.e. gangliogliomas (GG). To date the mechanisms underlying both, the altered neuronal architecture and the high epileptogenicity of the focal lesion, are still unresolved. Recently, we have identified a protein, Ste20-like kinase (SLK), a regulator of cytoskeletal dynamics in non-neuronal cells, that exhibits a strongly decreased expression in dysplastic neurons in surgical biopsy tissue of both FCDII and of GGs. However so far SLK’s function has not been studied in neurons. In this project, we will apply in vitro and in vivo techniques to examine how SLK contributes to regulate organization and function of neuronal networks in and in the penumbra of epileptogenic lesions.