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 sharp electrode and patch clamp recordings, and for measuring activity with calcium-indicator dyes and two-photon microscopy.

We have recently characterized interneuronal differentiation in mice overexpressing activated p21 ras (in cooperation with Prof Heumann at RUB) and developing rat visual cortex in vivo and in vitro. We have defined critical periods for molecular-neurochemical plasticity which depend on the environment, like afferent or reciprocal innervation, action potential activity, or the presence of 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 ). In projects currently under investigation (in cooperation with Prof Hollmann at RUB) we sought to unravel the role of AMPA-type glutamate receptors which are known to have specific biophysical properties. We found that specific splice and editing variants when overexpressed evoke an increase in the complexity of interneuronal dendrites and pyramidal cell apical dendrites, and also in spine building (see press release ). NMDA receptors and calcium channels are involved, and their contribution is under investigation.