The multifaceted subventricular zone astrocyte: From a metabolic and pro-neurogenic role to acting as a neural stem cell.

A few decades ago it was discovered that two regions of the adult brain retain the ability to generate new neurons. These regions include the subgranular zone of the hippocampal dentate gyrus and the ventricular-subventricular zone (V-SVZ) located at the border of the lateral ventricle. In the V-SVZ, it was discovered that neural progenitor cells (NPCs) share many features of mature astrocytes and are often referred as V-SVZ astrocytes. We will first describe the markers, the morphology, and the neurophysiological characteristics of the mouse V-SVZ astrocytes. We will then discuss the fact that V-SVZ astrocytes constitute a mixed population with respect to their neurogenic properties, e.g., quiescent versus activated state, neurogenic fate, and transcription factors expression. Finally, we will describe two functions of V-SVZ astrocytes, their metabolic coupling to blood vessels and their neurogenic-supportive role consisting of providing guidance and survival cues to migrating newborn neurons.

Na+ channel-mediated Ca2+ entry leads to glutamate secretion in mouse neocortical preplate.

Before synaptogenesis, early excitability implicating voltage-dependent and transmitter-activated channels is known to be crucial for neuronal development. We previously showed that preplate (PP) neurons of the mouse neocortex express functional Na(+) channels as early as embryonic day 12. In this study, we investigated the role of these Na(+) channels in signaling during early development. In the neocortex of embryonic-day-13 mice, activation of Na(+) channels with veratridine induced a large Ca(2+) response throughout the neocortex, even in cell populations that lack the Na(+) channel. This Na(+)-dependent Ca(2+) activity requires external Ca(2+) and is completely blocked by inhibitors of Na(+)/Ca(2+) exchangers. Moreover, veratridine-induced Ca(2+) increase coincides with a burst of exocytosis in the PP. In parallel, we show that Na(+) channel stimulation enhances glutamate secretion in the neocortical wall. Released glutamate triggers further Ca(2+) response in PP and ventricular zone, as indicated by the decreased response to veratridine in the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and NMDA-receptor inhibitors. Therefore, the combined activation of the Na(+) channel and the Na(+)/Ca(2+) exchanger triggers Ca(2+) signaling in the PP neurons, leading to glutamate secretion, which amplifies the signal and serves as an autocrine/paracrine transmitter before functional synapses are formed in the neocortex. Membrane depolarization induced by glycine receptors activation could be one physiological activator of this Na(+) channel-dependent pathway.