Neonatal and Adult Neurogenesis Provide Two Distinct Populations of Newborn Neurons to the Mouse Olfactory Bulb

Abstract

In mammals, the olfactory bulb (OB) constitutes one of two regions of the postnatal brain with continuous neurogenesis throughout life. Despite intense explorations of neuronal replacement in the adult OB, little is known about the mechanisms that operate at earlier postnatal stages. This question is particularly pertinent, because the majority of local interneurons are born in the neonate, when olfaction controls vital functions. Here, we analyzed the recruitment of newborn cells to the granule cell (GC) layer (GCL) and found that the postnatal mouse OB is supplied with two spatiotemporally distinct populations of newborn interneurons.Early born [postnatal day 3 (P3) to P7] GCs constitute a threefold larger population compared with those generated later (P14 -P60), and some of them are produced locally within the OB itself. Newborn interneurons generated at P3-P7 were predominantly targeted to the external edge of the GCL, whereas newly generated cells were positioned deeper in older mice. Additionally, although ϳ50% of adult newborn cells were eliminated within a few weeks of reaching the OB, almost the entire population of early born GCs survived until adulthood. Importantly, early olfactory experience specifically modifies the number of newborn GCs in neonates but leaves unaltered the amount of neurons generated during adulthood. Together, these results demonstrate that early postnatal neurogenesis endows the neonate bulbar circuit with newborn GCs that differ morphologically and functionally from those produced in the adult.

Sequential development of synapses in dendritic domains during adult neurogenesis

“…Whereas most of the postmigratory new neurons added into the bulb of newborns survive (33), only half of these neurons generated in the adult stably integrate and survive (33,34). Interestingly, the peak of adultgenerated GC death (33,34) occurs between the time when glutamatergic synapses first appear in the proximal domain and when these new neurons reach their final density of distal input-output synapses. The main period of cell death thus precedes the development of output synapses in adult-generated neurons.…”

Lentiviral Vectors Mediate Efficient and Stable Gene Transfer in Adult Neural Stem Cells In Vivo

“…The increase in transduced neurons in the olfactory bulb can be explained only by a continuous migration and differentiation of cells, originating from the SVZ, that constitutively divide and express eGFP after a single delivery of lentiviral vector. Whereas most of the ␥-aminobutyric acid (GABA)-ergic interneurons in the olfactory bulb are generated early after birth, about 2% are generated during a period ranging from the third postnatal week to adulthood (Bayer, 1983;Mirich et al, 2002;Lemasson et al, 2005). A large proportion of these bulbar interneurons generated in adulthood undergo cell death a few weeks after arrival in the OB (Petreanu and Alvarez-Buylla, 2002;Winner et al, 2002;Lemasson et al, 2005).…”

Spatio-temporal specification of olfactory bulb interneurons

“…In the early postnatal (Luskin 1993 ) and adult rodent (Lois and Alvarez-Buylla 1994 ) OB interneuron precursors are mainly generated in the SVZ of the lateral ventricle that develops from residual progenitors of the embryonic LGE and maintains neurogenic activity throughout life. Similarly to the embryos, a small proportion of early newlyborn postnatal OB interneurons are produced locally within the OB (Lemasson et al 2005 ). From their site of origin in the SVZ, interneuron precursors migrate tangentially along the rostral migratory stream (RMS) to reach the OB where they complete their differentiation (Alvarez-Buylla and Garcia-Verdugo 2002 ).…”

“…Recent findings suggest that the potentiality of SVZ progenitors is modulated in time and that specific subtypes of PG and GC interneurons are generated at different ages (Lemasson et al 2005 ;De Marchis et al 2007 ). Two spatio/temporally distinct populations of newborn neurons integrate into the OB GCL.…”

“…Two spatio/temporally distinct populations of newborn neurons integrate into the OB GCL. Indeed, early born granule cells (P3-P7) constitute a larger population, predominantly target to the external GCL, whereas newly generated cells in older mice were positioned deeper in the GCL (Lemasson et al 2005 ). We recently showed that the potentiality of SVZ progenitors is modulated in time and specific neurochemical classes of PG interneurons are generated at different ages (De Marchis et al 2007 ).…”