15 Maturation and Functional Integration of New Granule Cells into the Adult Hippocampus

Abstract

The hippocampus, located within the medial temporal lobe of the cerebral cortex, is critically important for the formation of semantic and episodic memory (Squire et al. 2004). As with other cortical circuits, the hippocampal network (Fig. 1) is highly dynamic and has the capacity to modify its connectivity by changing the number and strength of synaptic contacts in an activity-dependent manner. Synaptic connections can be added, strengthened, weakened, or eliminated in response to neuronal activity, a phenomenon called synaptic plasticity. The plasticity of specific hippocampal synapses has a significant role in memory formation and learning of hippocampus-dependent tasks (Nakazawa et al. 2004; Whitlock et al. 2006). The dentate gyrus (DG) of the adult hippocampus has the additional capacity of modifying the circuitry by the addition of new neurons. Thus, network remodeling is not limited to synapses, but also includes the incorporation of new functional units (neurons) that provide an additional dimension of plasticity to the existing hippocampal circuitry (Schinder and Gage 2004; Song et al. 2005; Lledo et al. 2006; Piatti et al. 2006).

The biological significance of adult hippocampal neurogenesis depends on the extent to which adult-born neurons can participate in signal processing in the hippocampal network. The impact of new neurons on the adult neuronal circuitry will be highly determined by how they become engaged in network activity and how their intrinsic properties and connectivities compare to those of existing dentate granule cells (GCs) that were generated during development. To list some possibilities, adult-born neurons could be continuously...