Neurogenesis in the Adult Hippocampus

Abstract

Of the neurogenic zones in the adult brain, adult hippocampal neurogenesis attracts the most attention, because it is involved in higher cognitive function, most notably memory processes, and certain affective behaviors. Adult hippocampal neurogenesis is also found in humans at a considerable level and appears to contribute significantly to hippocampal plasticity across the life span, because it is regulated by activity. Adult hippocampal neurogenesis generates new excitatory granule cells in the dentate gyrus, whose axons form the mossy fiber tract that links the dentate gyrus to CA3. It originates from a population of radial glia-like precursor cells (type 1 cells) that have astrocytic properties, express markers of neural stem cells and divide rarely. They give rise to intermediate progenitor cells with first glial (type 2a) and then neuronal (type 2b) phenotype. Through a migratory neuroblast-like stage (type 3), the newborn, lineage-committed cells exit the cell cycle and enter a maturation stage, during which they extend their dendrites into a the molecular layer and their axon to CA3. They go through a period of several weeks, during which they show increased synaptic plasticity, before finally becoming indistinguishable from the older granule cells.

Figure 1.

Developmental stages in the course of adult hippocampal neurogenesis (see text for details). GFAP, Glial fibrillary acidic protein; BLBP, brain lipid-binding protein; DCX, doublecortin; PSA-NCAM, polysialilated neural-cell-adhesion molecule; LTP, long-term potentiation.

Figure 2.

Dendrite development of newborn neurons in the dentate gyrus. Proliferating precursor cells in the subgranular zone (SGZ) were labeled with a green fluorescent protein (GFP)-expressing retrovirus and analyzed at later time points. Here, GFP-positive new granule cells can be seen at ∼2 wk (16 d after injection, left) and 4 wk (28 d after injection, right). During the early postmitotic maturation phase, the cells develop the full morphology of hippocampal granule cells. It is noteworthy that the cells might show a slightly different pace of maturation. After 4 wk, many cells have extended its dendritic tree far into the molecular layer. First dendritic spines can be seen on the dendrites (see Zhao et al. 2006, for details of dendritic development in adult hippocampal neurogenesis). Scale bar, 15 µm. (The figure is contributed by Chunmei Zhao, Salk Institute.)