New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?

Abstract

The dentate gyrus in the hippocampus in one of the discrete regions in which new neurons are continuously generated and integrated into local networks in the brains of adult mammals, including humans. Studies in the past decade have led to an understanding of the process of neurogenesis in the dentate gyrus; however, the functions of adult-born dentate granule cells (DGCs) remain unclear. After birth, adult-born DGCs undergo a lengthy process of morphogenesis including the de novo growth of axons and dendrites and the formation of both efferent and afferent synapses. The adult-born DGCs show enhanced excitability and plasticity before they are fully integrated into the brain circuitry. The addition of adult-born DGCs into the local network is extensively regulated by the experiences of the animal, which evoke hippocampal activity. Physiological and pathological conditions that alter hippocampal activity also affect adult neurogenesis in the hippocampus. The experiences of animals, especially those occurring during the maturation of DGCs, can influence the responsiveness of these cells when they become fully mature. A common hypothesis emerging from several computational studies is that adult neurogenesis allows plasticity to be mostly localized to newborn immature DGCs, preserving the information that is represented by mature DGCs. A recent model further proposes that immature DGCs can serve as a pattern integrator by linking events that occur closely in time. Studies combining neurogenesis ablation models with behavioural analyses have yielded inconsistent data concerning the functions of adult hippocampal neurogenesis. Besides the differences in specific experimental conditions, the varied experimental timelines and the types of function assessed are two major reasons for these discrepancies. The dentate gyrus plays a crucial role in pattern separation. A role for adult neurogenesis in pattern separation as a function of pattern similarity has recently been revealed. In the future, novel methods that have the cellular and temporal precision to manipulate neurogenesis and behavioural tests that directly assess dentate gyrus-related functions will be required to understand the functional mechanisms of adult neurogenesis.