AG Entwicklungsneurobiologie

AG Entwicklungsneurobiologie

Members

Scientific Staff


Dr. Mohammad Hamad ND 6/73 +49-(0)234-32-24344 E-Mail

PhD Students , Students (Diploma, Master, Bachelor)


Janine Neumann ND 6/73 +49-(0)234-32-24344 E-Mail
Kathrin Fielitz ND 6/66 +49-(0)234-32-24346 E-Mail

Nonscientific Personnel


Gabriele Dirscherl ND 6/66 +49-(0)234-32-24346 E-Mail
Andrea Räk ND 6/66 +49-(0)234-32-24346 E-Mail
Christian Riedel ND 6/66 +49-(0)234-32-24346 E-Mail
Sabine Schönfelder ND 6/66 +49-(0)234-32-24346 E-Mail

Research interests

A major property of nerve cells in the brain is their great variety in shape, function and neurochemistry. Our major research topic is the phenotype specification of interneurons in mammalian visual cortex. Cortical interneurons display a wealth of distinct morphologies especially axonal projection patterns, of electrophysiological firing patterns, and of neurochemical phenotypes. The question is how are these diverse neuron types specified during ontogenesis? We are using organotypic "roller tube" cultures as a model system. We found that the morphology and the firing patterns develop in an organotypic manner in cortex monocultures, likely because intrinsic factors are sufficient to drive the differentiation (Oliver Klostermann, Petra Wahle).
In contrast, certain neurochemical features depend on epigenetic/environmental factors. Neuronal activity for instance is required to upregulate Neuropeptide Y (NPY) mRNA expression in many neurons. Of the neurotrophins, only neurotrophin-4/5 (NT-4/5) but not brain-derived neurotrophic fator (BDNF), and to a certain degree also the cytokine Leukemia inhibiting factor (LIF) is able to activate NPY gene expression in the absence of activity (Marcus J. Wirth, Petra Wahle).
Afferences for instance from the thalamic lateral geniculate nucleus induce a phenotype shift in certain neuropeptidergic neurons which initially express NPY. When afferents are present many neurons gradually downregulate NPY mRNA expression during postnatal ontogenesis. A crucial factor is LIF. Its expression in the cortex is downregulated by the ingrowing afferents. Differentiating interneurons compete for LIF during a newly identified early postnatal period of molecular plasticity. They will stabilize NPY expression with sufficient LIF signalling. Without LIF however, many will transiently express NPY, but lateron downregulate and stop the expression. The 'losers' of the competition are parvalbuminergic basket and chandelier neurons, which in the adult are void of neuropeptides. Of the neurotrophins, only NT-4/5 but not BDNF, neurotrophin-3 or nerve growth factor, are able to stabilize the NPY phenotype. However, both NT-4/5 and BDNF, but not LIF, upregulate NPY expression in 'adult' cocultures in an activity- and use-dependent way (Kirstin Obst-Pernberg, Thorsten Gorba, Marcus J. Wirth, Petra Wahle)

We are currently analyzing the role of LIF and of the neurotrophins on phenotype expression in rat visual cortex in vivo in the course of the critical period. For instance, LIF infusion by osmotic minipumps clearly evoke neuropeptide expression, and it has effects on the maturation of visual parameters like development of receptive field size (Maren Engelhardt, Diploma thesis, Petra Wahle; in collaboration with Nicoletta Berardi, Graziella di Cristo, Lamberto Maffei, CNR, Pisa, Italy).

Other ongoing projects analyze the role of neuronal activity, afferent innervation and trophic factors on the expression of the two Glutamic acid decarboxylase (GAD) mRNAs and protein isoforms, the rate limiting enzymes for the ynthesis of the inhibitory transmitter gamma-amino butyric acid, and on the expression of the calcium-binding protein parvalbumin. While parvalbumin expression appears to depend only on neuronal activity, the two GADs are differentially influenced by activity and trophic factors on the transcriptional and translational level (Silke Patz, Marcus J. Wirth, Thorsten Gorba, Petra Wahle). We recently started to analyze the intracellular signalling cascade downstream to the neurotrophin receptors looking for differential effects on e.g. MAP kinase activation by neurotrophins in the presence and absence of activity (Jochen Grabert, Christian Riedel, Petra Wahle).

A second line of projects analyzes the role of neurotrophins and LIF for the structural differentiation of cortical neuron types. Marcus J. Wirth has established in the lab the technique of biolistic transfection with a hand-held gene gun device on rodent tissue. Neurons are transfected with plasmid DNA to overexpress trophic factors plus a reporter gene like Green Fluorescent Protein. The development of dendritic and axonal parameters of the transfectants will be analyzed (Marcus J. Wirth, Silke Patz, Andrea Driller, Petra Wahle)


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