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

The integration of adult-born neurons into the circuitry of the adult hippocampus suggests an important role for adult hippocampal neurogenesis in learning and memory, but its specific function in these processes has remained elusive. In this article, we summarize recent progress in this area, including advances based on behavioural studies and insights provided by computational modelling. Increasingly, evidence suggests that newborn neurons might be involved in hippocampal functions that are particularly dependent on the dentate gyrus, such as pattern separation. Furthermore, newborn neurons at different maturation stages may make distinct contributions to learning and memory. In particular, computational studies suggest that, before newborn neurons are fully mature, they might function as a pattern integrator by introducing a degree of similarity to the encoding of events that occur closely in time.

[1]  J. Altman,et al.  Post-Natal Origin of Microneurones in the Rat Brain , 1965, Nature.

[2]  D Marr,et al.  Simple memory: a theory for archicortex. , 1971, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[3]  J J Hopfield,et al.  Neural networks and physical systems with emergent collective computational abilities. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[4]  L. Voronin,et al.  Long-term potentiation in the hippocampus , 1983, Neuroscience.

[5]  C. B. Kanterman Something to chew on. , 1986, Tic.

[6]  B. McNaughton,et al.  Hippocampal synaptic enhancement and information storage within a distributed memory system , 1987, Trends in Neurosciences.

[7]  L. Squire Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. , 1992, Psychological review.

[8]  E T Rolls,et al.  Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network , 1992, Hippocampus.

[9]  B. McNaughton,et al.  Spatial selectivity of unit activity in the hippocampal granular layer , 1993, Hippocampus.

[10]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[11]  H. Cameron,et al.  Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat , 1993, Neuroscience.

[12]  James L. McClelland,et al.  Hippocampal conjunctive encoding, storage, and recall: Avoiding a trade‐off , 1994, Hippocampus.

[13]  T. Seki,et al.  Age‐related production of new granule cells in the adult dentate gyrus , 1995, Neuroreport.

[14]  E. Rolls A theory of hippocampal function in memory , 1996, Hippocampus.

[15]  F. Gage,et al.  More hippocampal neurons in adult mice living in an enriched environment , 1997, Nature.

[16]  D. Geschwind,et al.  Dentate Granule Cell Neurogenesis Is Increased by Seizures and Contributes to Aberrant Network Reorganization in the Adult Rat Hippocampus , 1997, The Journal of Neuroscience.

[17]  F. Gage,et al.  Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus , 1999, Nature Neuroscience.

[18]  E. Gould,et al.  Learning enhances adult neurogenesis in the hippocampal formation , 1999, Nature Neuroscience.

[19]  E. Gould,et al.  Neurogenesis in adulthood: a possible role in learning , 1999, Trends in Cognitive Sciences.

[20]  T J Sejnowski,et al.  Running enhances neurogenesis, learning, and long-term potentiation in mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[21]  T. Madsen,et al.  Electroconvulsive stimuli enhance both neuropeptide Y receptor Y1 and Y2 messenger RNA expression and levels of binding in the rat hippocampus , 2000, Neuroscience.

[22]  Eric J. Nestler,et al.  Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus , 2000, The Journal of Neuroscience.

[23]  E. Gould,et al.  Neurogenesis in the adult is involved in the formation of trace memories , 2001, Nature.

[24]  Paul E. Gilbert,et al.  Dissociating hippocampal subregions: A double dissociation between dentate gyrus and CA1 , 2001, Hippocampus.

[25]  G. Buzsáki,et al.  Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo , 2002, Nature Neuroscience.

[26]  E. Gould,et al.  Neurogenesis may relate to some but not all types of hippocampal‐dependent learning , 2002, Hippocampus.

[27]  E. Gould,et al.  Granule neurons generated during development extend divergent axon collaterals to hippocampal area CA3 , 2002, The Journal of comparative neurology.

[28]  D. Abrous,et al.  Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date , 2003, Molecular Psychiatry.

[29]  T. Madsen,et al.  Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat , 2003, Neuroscience.

[30]  Hiroki Toda,et al.  Inflammatory Blockade Restores Adult Hippocampal Neurogenesis , 2003, Science.

[31]  G. Kempermann,et al.  Adult‐born hippocampal neurons mature into activity‐dependent responsiveness , 2003, The European journal of neuroscience.

[32]  John L. Baker Is there a support vector machine hiding in the dentate gyrus? , 2003, Neurocomputing.

[33]  Christoph Schmidt-Hieber,et al.  Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus , 2004, Nature.

[34]  S. Vandenberg,et al.  Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice , 2004, Experimental Neurology.

[35]  Jacob Raber,et al.  Radiation-Induced Cognitive Impairments are Associated with Changes in Indicators of Hippocampal Neurogenesis , 2004, Radiation research.

[36]  E. Gould,et al.  Learning Enhances the Survival of New Neurons beyond the Time when the Hippocampus Is Required for Memory , 2004, The Journal of Neuroscience.

[37]  F. Gage,et al.  A hypothesis about the role of adult neurogenesis in hippocampal function. , 2004, Physiology.

[38]  M. Sofroniew,et al.  GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain , 2004, Nature Neuroscience.

[39]  D. Lieberman Something to chew on , 2004, Nature.

[40]  R. Cuppini,et al.  Morpho-functional characterization of neuronal cells at different stages of maturation in granule cell layer of adult rat dentate gyrus , 2004, Brain Research.

[41]  Karl Deisseroth,et al.  Excitation-Neurogenesis Coupling in Adult Neural Stem/Progenitor Cells , 2004, Neuron.

[42]  W. Miranker,et al.  Simulated Apoptosis/Neurogenesis Regulates Learning and Memory Capabilities of Adaptive Neural Networks , 2004, Neuropsychopharmacology.

[43]  Laurenz Wiskott,et al.  Functional significance of adult neurogenesis , 2004, Current Opinion in Neurobiology.

[44]  A. F. Schinder,et al.  Neuronal Differentiation in the Adult Hippocampus Recapitulates Embryonic Development , 2005, The Journal of Neuroscience.

[45]  Willard L. Miranker,et al.  Apoptosis, neurogenesis, and information content in Hebbian networks , 2005, Biological Cybernetics.

[46]  G. Westbrook,et al.  GABAergic signaling to newborn neurons in dentate gyrus. , 2005, Journal of neurophysiology.

[47]  C. Rampon,et al.  New neurons in the dentate gyrus are involved in the expression of enhanced long‐term memory following environmental enrichment , 2005, The European journal of neuroscience.

[48]  B. McNaughton,et al.  Mapping behaviorally relevant neural circuits with immediate-early gene expression , 2005, Current Opinion in Neurobiology.

[49]  R. J. McDonald,et al.  A role for adult neurogenesis in spatial long-term memory , 2005, Neuroscience.

[50]  D. Dupret,et al.  Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus , 2005, The European journal of neuroscience.

[51]  S. Becker A computational principle for hippocampal learning and neurogenesis , 2005, Hippocampus.

[52]  Fred H. Gage,et al.  Exercise Enhances Learning and Hippocampal Neurogenesis in Aged Mice , 2005, The Journal of Neuroscience.

[53]  E. Rolls,et al.  A computational theory of hippocampal function, and empirical tests of the theory , 2006, Progress in Neurobiology.

[54]  E. Gould,et al.  Temporal Discontiguity Is neither Necessary nor Sufficient for Learning-Induced Effects on Adult Neurogenesis , 2006, The Journal of Neuroscience.

[55]  Janet Wiles,et al.  Potential role for adult neurogenesis in the encoding of time in new memories , 2006, Nature Neuroscience.

[56]  Hongjun Song,et al.  GABA regulates synaptic integration of newly generated neurons in the adult brain , 2006, Nature.

[57]  Chunmei Zhao,et al.  Distinct Morphological Stages of Dentate Granule Neuron Maturation in the Adult Mouse Hippocampus , 2006, The Journal of Neuroscience.

[58]  Fred H. Gage,et al.  NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus , 2006, Nature.

[59]  Jason S. Snyder,et al.  Inhibition of neurogenesis interferes with hippocampus‐dependent memory function , 2006, Hippocampus.

[60]  E. Kandel,et al.  Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus , 2006, Proceedings of the National Academy of Sciences.

[61]  G. Westbrook,et al.  Seizures Accelerate Functional Integration of Adult-Generated Granule Cells , 2006, The Journal of Neuroscience.

[62]  Carol A Barnes,et al.  Integration of New Neurons into Functional Neural Networks , 2006, The Journal of Neuroscience.

[63]  N. Barbaro,et al.  Aberrant seizure‐induced neurogenesis in experimental temporal lobe epilepsy , 2006, Annals of neurology.

[64]  Laurenz Wiskott,et al.  A functional hypothesis for adult hippocampal neurogenesis: Avoidance of catastrophic interference in the dentate gyrus , 2006, Hippocampus.

[65]  Guy M McKhann,et al.  Hippocampal Neurogenesis is not Required for Behavioral Effects of Environmental Enrichment. , 2006, Neurosurgery.

[66]  C. Rampon,et al.  Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus , 2006, The Journal of Neuroscience.

[67]  M. Jung,et al.  Enhanced proliferation of progenitor cells following long-term potentiation induction in the rat dentate gyrus , 2006, Neurobiology of Learning and Memory.

[68]  F. Gage,et al.  Seizure-Associated, Aberrant Neurogenesis in Adult Rats Characterized with Retrovirus-Mediated Cell Labeling , 2007, The Journal of Neuroscience.

[69]  S. Becker,et al.  A model of hippocampal neurogenesis in memory and mood disorders , 2007, Trends in Cognitive Sciences.

[70]  F. Gage,et al.  Experience-Specific Functional Modification of the Dentate Gyrus through Adult Neurogenesis: A Critical Period during an Immature Stage , 2007, The Journal of Neuroscience.

[71]  Mirjana Maletic-Savatic,et al.  Comment on "Magnetic Resonance Spectroscopy Identifies Neural Progenitor Cells in the Live Human Brain" , 2008, Science.

[72]  E. Kandel,et al.  Paradoxical influence of hippocampal neurogenesis on working memory , 2007, Proceedings of the National Academy of Sciences.

[73]  S. Ge,et al.  A Critical Period for Enhanced Synaptic Plasticity in Newly Generated Neurons of the Adult Brain , 2007, Neuron.

[74]  C. Houser Interneurons of the dentate gyrus: an overview of cell types, terminal fields and neurochemical identity. , 2007, Progress in brain research.

[75]  Comment on “potential role for adult neurogenesis in the encoding of time in new memories” , 2007, Hippocampus.

[76]  D. Amaral,et al.  The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). , 2007, Progress in brain research.

[77]  M. Moser,et al.  Pattern Separation in the Dentate Gyrus and CA3 of the Hippocampus , 2007, Science.

[78]  David Dupret,et al.  Spatial Learning Depends on Both the Addition and Removal of New Hippocampal Neurons , 2007, PLoS biology.

[79]  Afra H. Wang,et al.  Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus , 2007, Nature Neuroscience.

[80]  Fred H. Gage,et al.  Adult neurogenesis , 2007, Scholarpedia.

[81]  Fred H. Gage,et al.  An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus , 2007, Proceedings of the National Academy of Sciences.

[82]  K. Deisseroth,et al.  Circuit-breakers: optical technologies for probing neural signals and systems , 2007, Nature Reviews Neuroscience.

[83]  Mark Ellisman,et al.  Synapse formation on neurons born in the adult hippocampus , 2007, Nature Neuroscience.

[84]  M. Wilson,et al.  Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network , 2007, Science.

[85]  R. Kesner A behavioral analysis of dentate gyrus function. , 2007, Progress in brain research.

[86]  K. Deisseroth,et al.  optical technologies for probing neural signals and systems , 2007 .

[87]  J. Epp,et al.  Hippocampus-dependent learning promotes survival of new neurons in the dentate gyrus at a specific time during cell maturation , 2007, Neuroscience.

[88]  D. Dupret,et al.  Spatial Relational Memory Requires Hippocampal Adult Neurogenesis , 2008, PloS one.

[89]  T. Madsen,et al.  Electroconvulsive seizure restores neurogenesis and hippocampus‐dependent fear memory after disruption by irradiation , 2008, The European journal of neuroscience.

[90]  R. Hen,et al.  Hippocampal neurogenesis and depression. , 2008, Novartis Foundation symposium.

[91]  A. Bacci,et al.  The Timing of Differentiation of Adult Hippocampal Neurons Is Crucial for Spatial Memory , 2008, PLoS biology.

[92]  Susumu Tonegawa,et al.  Transgenic Inhibition of Synaptic Transmission Reveals Role of CA3 Output in Hippocampal Learning , 2008, Science.

[93]  Ju Young Kim,et al.  Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain , 2008, Proceedings of the National Academy of Sciences.

[94]  Jun-Hyeok Choi,et al.  Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory , 2009, Molecular Brain.

[95]  F. Gage,et al.  Neurons born in the adult dentate gyrus form functional synapses with target cells , 2008, Nature Neuroscience.

[96]  C. Stark,et al.  Pattern Separation in the Human Hippocampal CA3 and Dentate Gyrus , 2008, Science.

[97]  A. Kramer,et al.  Be smart, exercise your heart: exercise effects on brain and cognition , 2008, Nature Reviews Neuroscience.

[98]  Oiwi Parker Jones,et al.  A Computational Approach , 2008 .

[99]  M. Moser,et al.  Impaired Spatial Representation in CA1 after Lesion of Direct Input from Entorhinal Cortex , 2008, Neuron.

[100]  Fred H. Gage,et al.  A role for adult TLX-positive neural stem cells in learning and behaviour , 2008, Nature.

[101]  M. Grubb,et al.  Functional Maturation of the First Synapse in Olfaction: Development and Adult Neurogenesis , 2008, The Journal of Neuroscience.

[102]  T. Shimazaki,et al.  [Mammalian neural stem cells]. , 2008, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[103]  Ryoichiro Kageyama,et al.  Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain , 2008, Nature Neuroscience.

[104]  F. Gage,et al.  Mechanisms and Functional Implications of Adult Neurogenesis , 2008, Cell.

[105]  Armen Saghatelyan,et al.  Interneurons Produced in Adulthood Are Required for the Normal Functioning of the Olfactory Bulb Network and for the Execution of Selected Olfactory Behaviors , 2009, The Journal of Neuroscience.

[106]  M. Drew,et al.  Neurogenesis-Dependent and -Independent Effects of Fluoxetine in an Animal Model of Anxiety/Depression , 2009, Neuron.

[107]  Anirvan Ghosh,et al.  Krüppel-Like Factor 9 Is Necessary for Late-Phase Neuronal Maturation in the Developing Dentate Gyrus and during Adult Hippocampal Neurogenesis , 2009, The Journal of Neuroscience.

[108]  F. Gage,et al.  Adult-Born Hippocampal Dentate Granule Cells Undergoing Maturation Modulate Learning and Memory in the Brain , 2009, The Journal of Neuroscience.

[109]  F. Gage,et al.  Signaling in adult neurogenesis. , 2009, Annual review of cell and developmental biology.

[110]  P. Argibay,et al.  A putative role for neurogenesis in neurocomputational terms: Inferences from a hippocampal model , 2009, Cognition.

[111]  M. C. Marchetto,et al.  Environmental influence on L1 retrotransposons in the adult hippocampus , 2009, Hippocampus.

[112]  C. Greer,et al.  Adult neurogenesis and the olfactory system , 2009, Progress in Neurobiology.

[113]  S. Trouche,et al.  Recruitment of adult-generated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory , 2009, Proceedings of the National Academy of Sciences.

[114]  Takashi Kitamura,et al.  Adult Neurogenesis Modulates the Hippocampus-Dependent Period of Associative Fear Memory , 2009, Cell.

[115]  Jacques I Wadiche,et al.  Input-Specific GABAergic Signaling to Newborn Neurons in Adult Dentate Gyrus , 2009, The Journal of Neuroscience.

[116]  Jason S. Snyder,et al.  The effects of exercise and stress on the survival and maturation of adult‐generated granule cells , 2009, Hippocampus.

[117]  H. Praag Exercise and the brain: something to chew on , 2009, Trends in Neurosciences.

[118]  G. Kempermann,et al.  Adult-Generated Hippocampal Neurons Allow the Flexible Use of Spatially Precise Learning Strategies , 2009, PloS one.

[119]  L. Saksida,et al.  A Functional Role for Adult Hippocampal Neurogenesis in Spatial Pattern Separation , 2009, Science.

[120]  H. Scharfman,et al.  A role for hilar cells in pattern separation in the dentate gyrus: A computational approach , 2009, Hippocampus.

[121]  Jason S. Snyder,et al.  Adult-Born Hippocampal Neurons Are More Numerous, Faster Maturing, and More Involved in Behavior in Rats than in Mice , 2009, The Journal of Neuroscience.

[122]  F. Gage,et al.  GABA-cAMP Response Element-Binding Protein Signaling Regulates Maturation and Survival of Newly Generated Neurons in the Adult Hippocampus , 2009, The Journal of Neuroscience.

[123]  J. Leasure,et al.  Social isolation prevents exercise‐induced proliferation of hippocampal progenitor cells in female rats , 2009, Hippocampus.

[124]  C. Bardy,et al.  Adult neurogenesis promotes synaptic plasticity in the olfactory bulb , 2009, Nature Neuroscience.

[125]  Janet Wiles,et al.  Computational Influence of Adult Neurogenesis on Memory Encoding , 2009, Neuron.

[126]  Larry R Squire,et al.  Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. , 2009, Learning & memory.

[127]  Alexei L. Vyssotski,et al.  Early age-related changes in adult hippocampal neurogenesis in C57 mice , 2010, Neurobiology of Aging.

[128]  Ainhoa Berciano-Alcaraz,et al.  A computational approach of , 2010 .