Neurogenesis in the adult hippocampus

Kempermann, Gerd; Song, Hongjun; Gage, Fred H.

doi:10.1101/cshperspect.a018812

Cited by 1,072Neurogenesis and neuroplasticity mechanismsMemory and Neural MechanismsNeuroscience and Neuropharmacology Research

Neurogenesis in the adult hippocampus

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Kempermann, Gerd, Song, Hongjun, Gage, Fred H.·2015·Cold Spring Harbor Perspectives in Biology

DOI 10.1101/cshperspect.a018812PMC PMC4563705

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Abstract

Of the neurogenic zones in the adult brain, adult hippocampal neurogenesis attracts the most attention, because it is involved in higher cognitive function, most notably memory processes, and certain affective behaviors.Adult hippocampal neurogenesis is also found in humans at a considerable level and appears to contribute significantly to hippocampal plasticity across the life span, because it is regulated by activity.Adult hippocampal neurogenesis generates new excitatory granule cells in the dentate gyrus, whose axons form the mossy fiber tract that links the dentate gyrus to CA3.It originates from a population of radial glia-like precursor cells (type 1 cells) that have astrocytic properties, express markers of neural stem cells and divide rarely.They give rise to intermediate progenitor cells with first glial (type 2a) and then neuronal (type 2b) phenotype.Through a migratory neuroblast-like stage (type 3), the newborn, lineage-committed cells exit the cell cycle and enter a maturation stage, during which they extend their dendrites into a the molecular layer and their axon to CA3.They go through a period of several weeks, during which they show increased synaptic plasticity, before finally becoming indistinguishable from the older granule cells. Because it has turned out that adult neuro- genesis not only exists in the human hippocampus but even seems to be restricted to it (see Spalding et al. 2013;Bergmann et al. 2015), public and scientific attention to the phenomenon is soaring.In PubMed, search results for "adult neurogenesis" and "hippocampus" outnumber those for "adult neurogenesis" and "olfactory bulb" or "subventricular" by 3:1.This is no reason to neglect research on adult neurogenesis in the olfactory system, which is a necessary part of any holistic view on adult neuro-genesis, but reason enough to ask for the motifs behind this interest.The answer, presumably, is "function."Adult hippocampal neurogenesis adds particular functionality to the mammalian hippocampus and presumably is involved in cognitive functions that we consider to be essential for humans.There is a price to pay for this type of plasticity.Adult neurogenesis is a complex multistep process, not a simple event.This review deals with the description of this process and the restriction points at which regulation occurs.

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The dentate gyrus gives rise to excitatory DG granule cells, whereas the SVZ produces migrating cells that follow the RMS and differentiate into inhibitory OB granule cells in the olfactory bulb.
“The first gives rise to the excitatory DG granule cells, whereas the second produces migrating cells that follow the RMS and in the olfactory bulb differentiate into inhibitory OB granule cells72,84,85.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [84]
The Abstract (page unavailable) states that adult hippocampal neurogenesis produces excitatory granule cells in the dentate gyrus. The Precursor Cell Phase mentions an SVZ/olfactory-bulb system, but our copy does not say that SVZ-derived cells follow the RMS or differentiate into inhibitory olfactory-bulb granule cells. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Neurogenesis continues during adulthood in the dentate gyrus of the hippocampus and the subventricular zone, where new neurons are generated throughout life from stem cells.
“Neurogenesis continues during adulthood in two specific neurogenic niches, the dentate gyrus of the hippocampus and the subventricular zone (SVZ) adjacent to lateral ventricles, where new neurons are generated throughout life from stem cells (Kempermann et al., 2015;Lim and Alvarez-Buylla, 2016).”
From Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise (2018) · cites this paper as Kempermann et al., 2015
Reduction in PTB triggered radial glial-like cells to convert into new granular neurons through what appears to be the typical developmental process by which new hippocampal neurons mature during development and in young adult animals.
“reduction in PTB triggered radial glial-like cells to convert into new granular neurons through what appears to be the typical developmental process by which new hippocampal neurons mature during development39 and in young adult animals40.”
From Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB (2021) · cites this paper as [40]

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Functional Convergence of Neurons Generated in the Developing and Adult Hippocampus
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Cell fusion-independent differentiation of neural stem cells to the endothelial lineage
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Type‐2 cells as link between glial and neuronal lineage in adult hippocampal neurogenesis
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Adult‐born hippocampal neurons mature into activity‐dependent responsiveness
Jessberger, S., & Kempermann, G. (2003) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2003.02986.x · Cited by 330 · see citing works
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Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice
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Decreased neurogenesis after cholinergic forebrain lesion in the adult rat
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Adult neurogenesis in Humans
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Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date
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Distinct Modes of Neuron Addition in Adult Mouse Neurogenesis
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Unique Expression Patterns of Cell Fate Molecules Delineate Sequential Stages of Dentate Gyrus Development
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Morpho-functional characterization of neuronal cells at different stages of maturation in granule cell layer of adult rat dentate gyrus
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Natural variation and genetic covariance in adult hippocampal neurogenesis
Kempermann, G., Chesler, E. J., Lu, L., Williams, R. W., & Gage, F. H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510291103 · Cited by 205 · see citing works
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Seizures preferentially stimulate proliferation of radial glia‐like astrocytes in the adult dentate gyrus: functional and immunocytochemical analysis
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Increased generation of granule cells in adult Bcl‐2‐overexpressing mice: a role for cell death during continued hippocampal neurogenesis
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Regulation of adult neurogenesis and plasticity by (early) stress, glucocorticoids, and inflammation.
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Spatial and temporal expression of short, long/medium, or both opsins in human fetal cones
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The vascular niche and its basement membrane
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GABA depolarization is required for experience-dependent synapse unsilencing in adult-born neurons
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Enriched Monolayer Precursor Cell Cultures from Micro-Dissected Adult Mouse Dentate Gyrus Yield Functional Granule Cell-Like Neurons
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Evidence that late-generated granule cells do not simply replace earlier formed neurons in the rat dentate gyrus
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Generation of Functional Inhibitory Neurons in the Adult Rat Hippocampus
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Phenotypic and Functional Characterization of Human LEUI (CD5) B Cells
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Targeted transgene expression in neuronal precursors: watching young neurons in the old brain
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Learning may reduce neurogenesis in adult rat dentate gyrus
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Seven principles in the regulation of adult neurogenesis
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Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity
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Chronic cocaine exposure impairs progenitor proliferation but spares survival and maturation of neural precursors in adult rat dentate gyrus
Domínguez‐Escribá, L., Hernández‐Rabaza, V., Soriano‐Navarro, M., Barcia, J. A., Romero, F. J., García‐Verdugo, J. M., & Canales, J. J. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04924.x · Cited by 100 · see citing works
Adult Hippocampal Neurogenesis in Natural Populations of MammalsPreprint
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Opposing Regulation of Sox2 by Cell-Cycle Effectors E2f3a and E2f3b in Neural Stem Cells
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GFAP-expressing radial glia-like cell bodies are involved in a one-to-one relationship with doublecortin-immunolabeled newborn neurons in the adult dentate gyrus
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Expression of the transcription factor Pax6 in the adult rat dentate gyrus
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Adult neurogenesis: an evolutionary perspective
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Detection and Phenotypic Characterization of Adult NeurogenesisPreprint
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Chondroitin sulfate proteoglycan expression pattern in hippocampal development: Potential regulation of axon tract formation
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Transcription-Factor-Dependent Control of Adult Hippocampal NeurogenesisPreprint
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p63 Regulates Adult Neural Precursor and Newly Born Neuron Survival to Control Hippocampal-Dependent Behavior
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Working memory training decreases hippocampal neurogenesis
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Proliferative response of distinct hippocampal progenitor cell populations after cortical infarcts in the adult brain
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Adult hippocampal neurogenesis and plasticity in the infrapyramidal bundle of the mossy fiber projection: I. Co-regulation by activity
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The Pessimist's and Optimist's Views of Adult Neurogenesis
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Control of Cell Survival in Adult Mammalian NeurogenesisPreprint
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Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus
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A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
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Chronic stress followed by social isolation promotes depressive-like behaviour, alters microglial and astrocyte biology and reduces hippocampal neurogenesis in male mice
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Authors: Kempermann, G., Song, H., & Gage, F. H.
Affiliations: Center for Regenerative Therapies Dresden (DE)
Johns Hopkins University (US)
Salk Institute for Biological Studies (US)
ORCID: Kempermann, Gerd
Song, Hongjun
Gage, Fred H.
Venue: Cold Spring Harbor Perspectives in Biology
Publisher: Cold Spring Harbor Laboratory
Published: 2015-09
Volume: 7
Issue: 9
Pages: a018812
ISSN: 1943-0264 (ISSN-L)
DOI: 10.1101/cshperspect.a018812
PMC: PMC4563705
OpenAlex: W2115290127
Cited by: 1,072
References: 158
Citations by year: 2026: 62 · 2025: 85 · 2024: 110 · 2023: 93 · 2022: 88 · 2021: 110 · 2020: 90 · 2019: 76 · 2018: 83 · 2017: 89 · 2016: 71 · 2015: 17 · 2014: 10 · 2013: 13 · 2012: 11
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Cold Spring Harbor Perspectives in Biology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DZNE Pub (submittedVersion)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: adult hippocampal neurogenesis, dentate gyrus granule cells, intermediate progenitor cells, neuronal maturation, synaptic plasticity, hippocampal plasticity, memory, emotional behavior, olfactory bulb neurogenesis, subventricular zone, neural stem cells, activity-dependent regulation
MeSH terms: Cell Survival, Hippocampus, Humans, Mitosis, Neurons, Neurogenesis

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