AMPA receptor activation leads to neurite retraction in tangentially migrating neurons in the intermediate zone of the embryonic rat neocortex

In rat (Konig et al, [1998] 28th Annual Meeting of the Society of Neuroscie nce, Los Angeles. 24:314.6) and mouse (Metin et al, [2000] J. Neurosci. 20: 696-708), neurons migrating tangentially in the intermediate zone (IZ) of t he neocortical anlage express functional AMPA receptors permeable to calciu m. The role of these receptors is as yet unknown. We exposed organotypic cu ltures of rat telencephalon (embryonic day 15) to AMPA receptor agonists or antagonists, and analyzed the effects of these treatments on cells in the IZ labeled with antibodies against the isoforms a, b and c of microtubule a ssociated protein 2 (MAP2) and the polysialylated neural cell adhesion mole cule (PSA-NCAM). The presence of functional AMPA receptors permeable to cal cium was checked by cobalt-loading. After exposure to AMPA alone for at lea st 6 hr, we observed a significant increase in the number of rounded, MAP2 positive cells in the IZ close to the migratory front. When AMPA was combin ed with cyclothiazide, the increase was already significant after 3 hr. The se effects were dose-dependent and could be partially or totally blocked by DNQX or GYKI 53655 respectively, that suggests that they are mediated by A MPA receptors. Paracrine AMPA receptor activation might participate, togeth er with other signals, in guiding the migratory stream, or provide stop sig nals for migrating cells. (C) 2001 Wiley-Liss, Inc.