A symphony of signals conducts early and late stages of adult neurogenesis

Abstract

Neurogenesis is continually occurring in two regions within the mammalian central nervous system (CNS) and increasing evidence suggests that it is important for selective learning and memory. How this plasticity is maintained in isolated niches within mature networks has been extensively studied in recent years, and a large body of evidence has accumulated describing many different regulatory factors and points of regulation. In this review, we attempt to organize the current research by summarizing findings affecting early neurogenesis: during proliferation, fate commitment and migration, versus late neurogenesis: including dendritic development, synaptic integration, and survival. We discuss the roles of three different classes of factors regulating early and late phases of neurogenesis: intrinsic factors, extrinsic factors, and neurotransmitters. Finally, we suggest that neurotransmitters may act upstream from extracellular other factors and cell-intrinsic mechanisms by coupling network activity to the niche microenvironment and intracellular machinery to ultimately regulate neurogenesis.

Figure 1

Neurogenesis persists in two regions of the postnatal brain: the subventricular zone (SVZ) lining the lateral ventricles (orange) and the subgranular zone (SGZ) of the dentate gyrus. Stem cell-like astrocytes in both regions are positive for glial-fibrillary acidic protein (GFAP) and divide to produce doublecortin-positive (DCX) neuroblasts. Once the neuroblasts arrive at their target destinations, in the granule or periglomerular layers in the olfactory bulb, or within the granule cell layer in the dentate gyrus, they elaborate their dendritic arbors, form synapses, and mature into neurons capable of producing action potentials. In the olfactory bulb the granule neurons (red) form GABAergic synapses onto mitral and tufted cells, while periglomerular neurons (green) form dopaminergic synapses on mitral and tufted cells and olfactory receptor neurons within and between glomeruli. In the dentate gyrus, granule neurons receive synaptic inputs onto their dendrites in the molecular layer from the entorhinal cortex, and send axons called mossy fibers that form glutamatergic synapses with neurons in CA3. EPL: external plexiform layer; GCL: granule cell layer ; LV: lateral ventricle; ML: molecular layer; OB: olfactory bulb; PG cell: periglomerular cell; TAC: Transit amplifying cell.

Figure 2

Table summarizing the affects of the different intracellular factors, extracellular factors and neurotransmitters on early phases of neurogenesis (proliferation, fate commitment, migration) versus late phases of neurogenesis (dendrite development, synaptic integration and survival) in the SVZ and SGZ. The numbers refer to references that are provided as Supplemental Material.