Kurzfassung

Neuronal migration is an essential process for the proper development of the the central nervous system. In the cerebral cortex, defects in neuronal migration are associated with pathologies resulting from neuronal migration disorders, e.g. like lissencephaly, and often induce neurological deficits (e.g. epilepsy, schizophrenia).

We have identified the GABA receptor as an essential component of the formation of the cortical layers in the newborn rat in vivo (Heck et al., 2007). In parallel, we...Neuronal migration is an essential process for the proper development of the the central nervous system. In the cerebral cortex, defects in neuronal migration are associated with pathologies resulting from neuronal migration disorders, e.g. like lissencephaly, and often induce neurological deficits (e.g. epilepsy, schizophrenia).

We have identified the GABA receptor as an essential component of the formation of the cortical layers in the newborn rat in vivo (Heck et al., 2007). In parallel, we could show an effect of GABA-A receptor activation on the migration rate in a neocortical slice culture model. The implication of GABA receptors in neuronal migration is clinically relevant, because most anaesthetics target the GABA system. The use of classical anaesthetics on pregnant women could thus have deleterious effects on the foetus.

We recently observed that ionotropic GABA receptors, the GABA-A and GABA-C receptors (Zhang et al., 2001;Bormann, 2000), have opposite roles on neuronal migration (Heck et al., in preparation). Since the expression of GABA-C receptors in the developing cerebral cortex has not yet been reported, we plan to characterize its expression and distribution.

Our previous study has shown that the activation of GABA receptors is linked with changes in intracellular calcium concentrations. Since calcium level dynamics is correlated with migration rate, we plan to measure calcium activity upon GABA activation (confocal calcium fluorescence imaging) and examine by the use of pharmacological agents which receptors and pathways are involved. In order to examine specifically the activity in migrating glutamatergic cells, the method of in utero electroporation will be establish in our laboratory. This powerful technique, which to our knowledge is not yet established in Mainz, allows the identification of migrating cells in vivo and in slice culture. Hence the role of both GABA-A and GABA-C in the regulation of calcium activation and cell migration will be specifically assessed in identified migrating glutamatergic neurons.


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