Adult neurogenesis in the rat olfactory bulb

In adult animals, neurons generated within the subventricular zone (SVZ), following the rostral migratory stream (RMS), reach the olfactory bulb (OB), where they apparently give rise to interneurons. In fact, there has never been a functional demonstration that these cells are true neurons. Filling this gap has been impeded largely by the inability to distinguish between newly generated cells (NGC) in living brain tissue using conventional approaches. We have solved this problem combining retrovirus-mediated genetransfer and patch-clamp electrophysiology. The viral vector, including a gene for GFP, was injected into the SVZ. After 2 weeks, GFP+ cells resembling periglomerular cells (PG) were observed in the OB. Using a whole-cell patch-clamp technique, we recorded action potentials from NGC in response to the injection of depolarizing currents, and we have isolated and characterized Na+ and K+ currents. About 95% of the NGC were PG cells; the remaining ended their migration between internal plexiform and mitral cell layers, and were identified as short-axon cells. The progressive maturation of NGC has been characterized in time and space along the RMS. When in the RMS, the cells show only a weak delayed rectifier K+-current, to which an A-current is added when the OB is reached. The mature cells lose the delayed rectifier K+-current, and only display A- and Na+-currents. Finally, by recording action potentials and excitatory synaptic currents in response to stimulation of the olfactory nerve, for the first time we have demonstrated that the NGC fully integrate into the bulbar circuitry, establishing functional synaptic contacts.