Functions and dysfunctions of adult hippocampal neurogenesis

Abstract

Adult neurogenesis, a developmental process of generating functionally integrated neurons, occurs throughout life in the hippocampus of the mammalian brain and showcases the highly plastic nature of the mature central nervous system. Significant progress has been made in recent years to decipher how adult neurogenesis contributes to brain functions. Here we review recent findings that inform our understanding of adult hippocampal neurogenesis processes and special properties of adult-born neurons. We further discuss potential roles of adult-born neurons at the circuitry and behavioral levels in cognitive and affective functions and how their dysfunction may contribute to various brain disorders. We end by considering a general model proposing that adult neurogenesis is not a cell-replacement mechanism, but instead maintains a plastic hippocampal neuronal circuit via the continuous addition of immature, new neurons with unique properties and structural plasticity of mature neurons induced by new-neuron integration.

Keywords: brain disorders; dentate gyrus; development; neural stem cells.

Figure 1

Summary of basic processes of neurogenesis in the young adult mouse hippocampus. (a) A sagittal section view of an adult rodent brain highlighting two restricted regions that exhibit active adult neurogenesis—the hippocampus (HP) and lateral ventricle (LV)—which generate new neurons that mostly migrate into the olfactory bulb. More detailed hippocampal structure is further illustrated with the primary trisynaptic circuit formed by three principal neuronal subtypes. (b) Summary of the developmental processes of adult hippocampal neurogenesis, including time course of marker expression, developmental stages, synaptic integration, and special neuronal properties associated with different stages. BC, basket cells; DG, dentate gyrus; EC, entorhinal cortex; HICAP, hilar interneuron with commissural-associational pathway-associated axon terminals; HIPP, hilar perforant path-associated interneurons; IPCs, intermediate progenitor cells; MOPP, molecular-layer perforant pathway cells; OB, olfactory bulb; PV⁺, parvalbumin-expressing interneurons; RGL, radial glia-like cell.

Figure 2

Circuitry properties of newborn neurons in the adult hippocampus. A schematic illustration of connectivity of newborn neurons in the adult dentate gyrus, highlighting the two modes by which newborn neurons can contribute to hippocampal functions, direct information processing via CA3 neurons (i, direct pathway) and modulation of local circuitry via hilar interneurons and mossy cells (ii, indirect pathway). GCL, granule cell layer; SST⁺ neurons, somatostatin-expressing interneurons.