14 The Balance of Trophic Support and Cell Death in Adult Neurogenesis

The fact that continuous proliferation of stem cells and progenitors, as well as the production of neurons, occurs in the adult CNS raises several basic questions concerning the number of neurons required in a particular system: Can we observe a continued growth of brain regions that sustain neurogenesis? Or does an elimination mechanism exist that keeps the number of cells constant? If so, are the old ones replaced or are the new neurons competing for limited network access? What signals would support their survival and integration and what factors are responsible for their elimination? This chapter addresses these and other questions regarding regulatory mechanisms affecting adult neurogenesis by controlling cell survival. ARE NEUROGENIC BRAIN REGIONS EXPANDING DESPITE SPACE LIMITATIONS? This question was initially addressed several decades ago, following the first evidence that adult mammalian neurogenesis exists. Total neuronal cell counts of the olfactory bulb (OB) and dentate gyrus (DG) at different ages revealed that in both regions, a continued growth of the granule cell layer occurs throughout adult life. From 1 month of age, when the developmental production of granule cells can be considered complete, until 1 year of age, the number of DG granule cells doubles in the rat (Bayer 1982; Bayer et al. 1982). A rise in total volume and increased cell density due to reduced cell diameter both contribute to this phenomenon. In the rat OB, a linear growth of the granule cell layer was observed with age (Kaplan et al. 1985), with the number of olfactory...