Heinz Beck (Department of Epileptology, Life & Brain Center, University of Bonn Medical Center)

Abstract:
Central neurons receive thousands of excitatory synapses onto synaptic spines emanating from their dendrites. To understand how individual neurons transform these inputs from their network partners to an output signal is a fundamental prerequisite to understand the function of neuronal networks. Our understanding of these integrative processes has been mainly confined to the somatic and proximal dendritic compartment of neurons. Due to technical problems in analyzing excitatory and inhibitory signal integration at more distal processes, the properties of the complex apical and basal higher order dendrites, which receive over 95% of the excitatory synaptic connections from other neurons, are incompletely understood. Moreover, despite the importance of higher order dendritic properties for neuronal function, potential changes in these properties have hitherto not been examined in any central nervous system disorder. Excitatory signal integration at small higher order dendrites can now be examined at unprecedented detail using multiphoton neurotransmitter uncaging, in particular multiphoton glutamate uncaging, in combination with electrophysiology and multiphoton imaging. This has already resulted in a significant improvement in our understanding of excitatory input integration in different hippocampal excitatory cells. In particular, they have shown that different hippocampal neurons are capable of fundamentally different integration modes. Application of these techniques to CNS disorders such as epilepsy is essential in understanding changes in input integration at distal dendrites.