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

Abstract

In rat (König et al. [1998] 28th Annual Meeting of the Society of Neuroscience, Los Angeles. 24:314.6) and mouse (Métin et al. [2000] J. Neurosci. 20:696-708), neurons migrating tangentially in the intermediate zone (IZ) of the neocortical anlage express functional AMPA receptors permeable to calcium. The role of these receptors is as yet unknown. We exposed organotypic cultures 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 associated protein 2 (MAP2) and the polysialylated neural cell adhesion molecule (PSA-NCAM). The presence of functional AMPA receptors permeable to calcium was checked by cobalt-loading. After exposure to AMPA alone for at least 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 combined with cyclothiazide, the increase was already significant after 3 hr. These effects were dose-dependent and could be partially or totally blocked by DNQX or GYKI 53655 respectively, that suggests that they are mediated by AMPA receptors. Paracrine AMPA receptor activation might participate, together with other signals, in guiding the migratory stream, or provide stop signals for migrating cells.