Review
Feature Review
Adult neurogenesis: integrating theories and separating functions

https://doi.org/10.1016/j.tics.2010.04.003Get rights and content

The continuous incorporation of new neurons in the dentate gyrus of the adult hippocampus raises exciting questions about memory and learning, and has inspired new computational models to understand the function of adult neurogenesis. These theoretical approaches suggest distinct roles for new neurons as they slowly integrate into the existing dentate gyrus network: immature adult-born neurons seem to function as pattern integrators of temporally adjacent events, thereby enhancing pattern separation for events separated in time; whereas maturing adult-born neurons possibly contribute to pattern separation by being more amenable to learning new information, leading to dedicated groups of granule cells that respond to experienced environments. We review these hypothesized functions and supporting empirical research and point to new directions for future theoretical efforts.

Section snippets

The challenge of new neurons

Although the nervous systems of other vertebrates exhibit varying degrees of widespread neurogenesis 1, 2, in mammals neurogenesis almost completely ceases after development, with only two regions retaining an ongoing incorporation of new neurons throughout life [3]. One of these regions, the olfactory bulb, is populated by neurons that were originally born in the sub-ventricular zone (SVZ). Immature neurons migrate from the SVZ and give rise to several local interneuron populations in the

The function of the DG in hippocampal processing

Despite its large number of neurons and key position in the hippocampal formation (Figure 1), the DG has not been investigated as extensively as the other principal hippocampal areas, the CA3 and CA1. Nevertheless, several functions have been proposed for the DG 15, 16, most prominently that it is responsible for the pattern separation of cortical inputs to the hippocampus. The separation, or decorrelation, of encoding events is believed to be important to avoid interference between memories

Direct functions of immature, adult-born neurons

New neurons do not arise from existing neurons but rather grow into the adult circuitry de novo, arising from a population of NPCs that reside in the subgranular zone (SGZ) of the DG [34]. Newly born neurons are entirely distinct from the mature DG neurons and must undergo a considerable growth process before becoming recognizable as GCs. While the maturation process is vital to the growing neurons’ survival, and shapes their ultimate characteristics, the properties of neurons at different

Long-term functions of adult-born neurons

Although the evidence regarding new neuron maturation is consistent with the theoretical effects of immature neurons on pattern separation described above, these functions alone are not sufficient to explain the lifelong persistence of adult-born neurons. While a fraction of the immature neurons that contribute to the aforementioned functions probably die before fully integrating into the network, the majority of these neurons seem to survive and eventually attain anatomical and physiological

Conclusions and future directions

This review seeks to link the current theoretical views on neurogenesis function with relevant experimental findings. These different approaches increasingly suggest that the role of neurogenesis is highly complex and affects multiple aspects of learning, as opposed to being a clearly definable function. This subtlety is potentially responsible for the large variance observed between neurogenesis behavioral studies (see [6] for more extensive discussion), and it will continue to present a

Acknowledgements

We would like to thank M.L. Gage for editorial comments on the manuscript. This work is funded by the James S. McDonnell Foundation, the Lookout Fund, the Kavli Institute for Brain and Mind, the NSF Temporal Dynamics of Learning Center, and the National Institutes of Health (MH-090258).

References (132)

  • S. Ge

    A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain

    Neuron

    (2007)
  • J.B. Aimone

    Computational influence of adult neurogenesis on memory encoding

    Neuron

    (2009)
  • V.I. Weisz et al.

    A putative role for neurogenesis in neuro-computational terms: inferences from a hippocampal model

    Cognition

    (2009)
  • S. Becker et al.

    A model of hippocampal neurogenesis in memory and mood disorders

    Trends Cogn. Sci.

    (2007)
  • J.S. Snyder

    A role for adult neurogenesis in spatial long-term memory

    Neuroscience

    (2005)
  • K. Deisseroth

    Excitation-neurogenesis coupling in adult neural stem/progenitor cells

    Neuron

    (2004)
  • J.F. Guzowski

    Mapping behaviorally relevant neural circuits with immediate-early gene expression

    Curr. Opin. Neurobiol.

    (2005)
  • E.T. Rolls et al.

    A computational theory of hippocampal function, and empirical tests of the theory

    Prog. Neurobiol.

    (2006)
  • V.H. Brun

    Impaired spatial representation in CA1 after lesion of direct input from entorhinal cortex

    Neuron

    (2008)
  • E. Gould

    Neurogenesis in adulthood: a possible role in learning

    Trends Cogn. Sci.

    (1999)
  • S.A. Goldman et al.

    Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain

    Proc. Natl. Acad. Sci. U. S. A.

    (1983)
  • G.K. Zupanc

    Adult neurogenesis and neuronal regeneration in the central nervous system of teleost fish

    Brain Behav. Evol.

    (2001)
  • A. Mouret

    Centrifugal drive onto local inhibitory interneurons of the olfactory bulb

    Ann. N. Y. Acad. Sci.

    (2009)
  • Deng, W. et al. (2010) New neurons and new memories: How does adult hippocampal neurogenesis affect learning and...
  • K. Fabel

    Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogeneis in mice

    Front. Neurosci.

    (2009)
  • D. Dupret

    Spatial learning depends on both the addition and removal of new hippocampal neurons

    PLoS Biol.

    (2007)
  • E. Gould

    Learning enhances adult neurogenesis in the hippocampal formation

    Nat. Neurosci.

    (1999)
  • S. Jessberger et al.

    Stem-cell-associated structural and functional plasticity in the aging hippocampus

    Psychol. Aging

    (2008)
  • J.L. Warner-Schmidt et al.

    Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment

    Hippocampus

    (2006)
  • T.J. Shors

    Neurogenesis may relate to some but not all types of hippocampal-dependent learning

    Hippocampus

    (2002)
  • M.D. Saxe

    Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus

    Proc. Natl. Acad. Sci. U. S. A.

    (2006)
  • J.J. Hopfield

    Neural networks and physical systems with emergent collective computational abilities

    Proc. Natl. Acad. Sci. U. S. A.

    (1982)
  • D.G. Amaral

    The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies)

    Prog. Brain. Res.

    (2007)
  • D.A. Coulter et al.

    Functional regulation of the dentate gyrus by GABA-mediated inhibition

    Prog. Brain Res.

    (2007)
  • D.A. Henze

    Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo

    Nat. Neurosci.

    (2002)
  • E.T. Rolls

    A theory of hippocampal function in memory

    Hippocampus

    (1996)
  • A. Treves et al.

    Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network

    Hippocampus

    (1992)
  • P.E. Gilbert

    Dissociating hippocampal subregions: double dissociation between dentate gyrus and CA1

    Hippocampus

    (2001)
  • I. Lee et al.

    Encoding versus retrieval of spatial memory: double dissociation between the dentate gyrus and the perforant path inputs into CA3 in the dorsal hippocampus

    Hippocampus

    (2004)
  • T.J. McHugh

    Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network

    Science

    (2007)
  • A. Bakker

    Pattern separation in the human hippocampal CA3 and dentate gyrus

    Science

    (2008)
  • J.K. Leutgeb

    Pattern separation in the dentate gyrus and CA3 of the hippocampus

    Science

    (2007)
  • T. Nakashiba

    Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning

    Science

    (2008)
  • T.V. Bliss et al.

    Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path

    J. Physiol.

    (1973)
  • H. Suh

    Signaling in adult neurogenesis

    Annu. Rev. Cell Dev. Biol.

    (2009)
  • M.S. Esposito

    Neuronal differentiation in the adult hippocampus recapitulates embryonic development

    J. Neurosci.

    (2005)
  • L.S. Overstreet-Wadiche

    Delayed development of adult-generated granule cells in dentate gyrus

    J. Neurosci.

    (2006)
  • S. Wang

    Heterogenous properties of dentate granule neurons in the adult rat

    J. Neurobiol.

    (2000)
  • C. Zhao

    Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus

    J. Neurosci.

    (2006)
  • N. Toni

    Synapse formation on neurons born in the adult hippocampus

    Nat. Neurosci.

    (2007)
  • Cited by (245)

    View all citing articles on Scopus
    *

    Contributed equally to this work.

    View full text