Research Topics
My research focuses on activity-dependent self-organization and structure-function-dependencies in neuronal networks.
Albeit coarsely instructed by genetic programs during early development, neuronal connectivity in the brain is considerably shaped by activity-dependent interactions between neurons impacting on their structural and functional differentiation. Synaptic and spiking activity, for instance, regulate neuronal migration, neurite field elaboration, synaptogenesis and the maturation of inhibition. A homeostatic regulation of activity is furthermore essential for neuronal survival and neurons failing to embed themselves sufficiently into a network are prone to apoptosis. Excess connectivity and activity, in turn, entails pruning of connections and may likewise trigger apoptosis. Hence, consistent with evolutionary optimization, functionally useless or disturbing neurons seem to be programmed to disintegrate if they fail to (re)align into the circuit. Accordingly, individual neurons seek to dynamically establish and maintain a morphological embedding that satisfies certain activity requirements.
The concrete rules mapping activity to morphogenic processes crucially impact on the self-organization of network architecture at microscopic to mesoscopic scales. In the developmental context, I am fascinated by the idea that stereotypical and functionally relevant architectural patterns may emerge, almost miraculously, from local neuronal interactions. With experimental in vitro networks and computational models, we investigate how changes in activity-dependent morphogenesis or in developmental conditions influence the evolution of network connectivity. Examples are research projects focusing on the morphogenic impact of neuronal migration, external stimulation or maturing inhibition on activity-dependent network self-organization in vitro using pharmacological, electrophysiological and optogenetic tools. We study the topological and functional consequences of altered network architecture by means of immunohistochemistry and morphological reconstruction, and by recording network and single neuron activity using micro-electrode arrays, patch-clamp and calcium imaging. We combine our experimental findings with reduced models of neuronal network growth or connectivity-dependent activity propagation to gain insight into the process of network-self-organization and into structure-function dependencies. Aware of the complex biochemical and genetic meshwork underneath, we aim to derive an abstracted mechanistic understanding of neuronal network self-organization, emerging activity dynamics and the functional consequences.
