AG Entwicklungsneurobiologie

Schwerpunkte in der Forschung (nur in Englisch)

My lab has a long-standing interest in the development of cortical interneurons, in particular in the activity-dependent mechanisms of structural and neurochemical maturation. Our most important experimental platform is the organotypic slice culture prepared from the newborn rat visual neocortex. It is a long-term surviving primary culture with neurons in an organotypical composition of cell types, with local wiring in a typical 3D structural environment, and spontaneous activity with a well balanced excitation and inhibition. These cultures are easy to manipulate with pharmacological tools via the medium, easy to transfect (we use a gene gun transfection) for studying the effects of genes on the maturation of the indivividual cell or the action on the neuronal network, and of course applicable for state of the art histology, biochemical-molecular analyses, and confocal imaging. Further, we have used the cultures successfully for recordings and for measuring activity with calcium-indicator dyes and two-photon/confocal microscopy.

We have defined critical periods for molecular-neurochemical plasticity which depend on the environment, such as afferent or reciprocal innervation, action potential activity, or the presence or absence of certain trophic factors (see press release ). We showed that the growth and branching of dendrites of pyramidal cells and interneurons can be mediated by the neurotrophic factors BDNF and NT4 in an autocrine fashion. We could show that neurotrophins become imported from a target area of an axonal projection and recycled in the cortex to local interneurons which in turn respond with an altered expression of neuropeptide Y, the brain's endogenous antiepileptic peptide (see press release ). More recently we could show that some variants of AMPA receptors, when overexpressed, evoke dendritic growth. We found that specific splice and editing variants when overexpressed evoke an increase in the complexity of pyramidal cell apical dendrites, and also in spine building (see press release ). Flip variants turned out to be more efficient than calcium-permeable receptor variants. Of the many tested variants only one was found to modify interneuronal dendrites. Overexpression of type-I TARPs which transport AMPA receptors to the membrane also caused dendritic growth of pyramidal neurons. Moreover, the effects are seen only in apical dendrites. In a recent study we found that basal dendrites of pyramidal cells depend on NMDA receptor signaling, in particular on GluN2B-containing receptors in a early time window of development. Surprisingly, also kainate receptors play a role for interneurons and pyramidal cells, after overexpression as well as via an increase in network activity (see press release ). Calcium signalling is crucial for dendrite growth. Modifying the calcium dynamics by expression of genetically encoded calcium indicators, which basically are calcium buffers, we found that some are substantially delaying differentiation and may evoke degeneration. Thus, these commonly used tools for calcium imaging can impair neuronal differentiation. In ongoing studies we ask if we could regulate neurite growth using chemogenetics (DREADDs) and optogenetics (channelrhodopsin). Finally, "from the forest to the lab", we are analyzing the fetal cortical development of a non-domesticated hoofed mammal, the wild boar (Sus scrofa), a precocious species with a rather short gestation period, but a large gyrated brain (see press release ).