Functional properties of adult-born juxtaglomerular cells in the mammalian olfactory bulb.

It is now generally acknowledged that two regions of the brain maintain the capacity to produce new cells in adulthood (Gross, 2000): throughout all postnatal life new neurons are added to the dentate gyrus of the hippocampus and to the olfactory bulb (OB) of all mammals (Hastings et al., 2000), including primates (Kornack and Rakic, 2001). In particular, neuroblasts bound to the OB originate in the more anterior part of the lateral ventricles, in a region called subventricular zone (SVZ), and migrate to the OB, where they end in the glomerular and granule cell layers (Alvarez-Buylla and Garcia-Verdugo, 2002; Winner et al., 2002). In order to establish that postnatally generated cells have become functional neurons three conditions should be met: first, it should be identified the point in time at or after which the cell was generated; secondly, evidence should be provided that the new cell has the functional properties of a neuron (e.g. capacity to generate action potentials); and thirdly, it should be demonstrated that the new cells are capable of entering into synaptic relationship with the existing neuronal network. This kind of evidence has been provided for cells generated in the SGZ in adult hippocampus, where it has been shown that the new cells differentiate into granule cells that integrate into hippocampal circuitry (van Praag et al., 2002). For the new cells generated in the SVZ, in contrast, direct experimental evidence of functionality is more limited (Carlén et al., 2002; Carleton et al., 2003). In the OB, postnatally generated interneurons have been well characterized morphologically, but very little is known concerning their physiology and function. Obtaining recordings from neurons identified as newly generated has been primarily impeded by the difficulty in distinguishing between previously generated and newly generated neurons in living brain tissue. Our experimental approach was to use replication-incompetent recombinant retrovirus to infect newly generated cells in the SVZ and genetically mark them with a reporter protein [an enhanced version of the green fluorescent protein, engineered with the membrane targeted domain of gap43 (Moriyoshi et al., 1996; Okada et al., 1999)]. Two to five days after virus injection GFP+ cells were found in the SVZ and in the rostral migratory stream (RMS). Time lapse imaging of labelled cells in RMS indicated that they were migratory neurons moving at the average speed of ~30 µm/h. After 10–14 days virally infected cells were found in the granular and glomerular …