Kurzfassung

During early development glutamatergic and GABAergic signaling systems become functioning before appropriate synapses are formed. Immature migrating neurons express both functional glutamate and GABA receptors that are activated by endogenous neurotransmitters. Both over-activation and blockade of either NMDA- or GABA_A-receptors induce neuronal migration disorders suggesting that extracellular glutamate and GABA play important roles in corticogenesis. But do they fulfill their functions...During early development glutamatergic and GABAergic signaling systems become functioning before appropriate synapses are formed. Immature migrating neurons express both functional glutamate and GABA receptors that are activated by endogenous neurotransmitters. Both over-activation and blockade of either NMDA- or GABA_A-receptors induce neuronal migration disorders suggesting that extracellular glutamate and GABA play important roles in corticogenesis. But do they fulfill their functions independently on each other? At the beginning of the present project, we made the observation that synaptic transmission at Cajal-Retzius neurons, a class of pioneer neurons in the marginal zone of the neocortex, is tonically inhibited by ambient GABA via presynaptic GABA_B receptors. The degree of this suppression is determined by GABA transporters (GAT-3), which are located on glial cells and operate in the reverse mode, i.e. releasing GABA. This observation was surprising, because glial cells do not express glutamate decarboxylase, the main GABA synthesizing enzyme. During the first funding period, we have shown that blockade of glutamate transporters, which are mainly located on glial cells, abolishes GABA_B receptor-meditated inhibition of GABAergic transmission. Therefore, we suggest that glial cells are responsible for the precise control of both extracellular glutamate and GABA levels. Moreover, we intend to demonstrate that Na⁺ dependent transporters on glial cells take up potentially excitotoxic and epileptogenic glutamate replacing it by also excitatory, but much less “dangerous” GABA. We hope that this project will afford a better understanding of glial contributions to cell-to-cell communications via extracellular space during the early development of the cerebral cortex.» weiterlesen» einklappen