Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus
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Adult neurogenesis in the dentate gyrus may contribute to hippocampus-dependent functions, yet little is known about when and how newborn neurons are functional because of limited information about the time course of their connectivity. By using retrovirus-mediated gene transduction, we followed the dendritic and axonal growth of adult-born neurons in the mouse dentate gyrus and identified distinct morphological stages that may indicate different levels of connectivity. Axonal projections of newborn neurons reach the CA3 area 10-11 d after viral infection, 5-6 d before the first spines are formed. Quantitative analyses show that the peak of spine growth occurs during the first 3-4 weeks, but further structural modifications of newborn neurons take place for months. Moreover, the morphological maturation is differentially affected by age and experience, as shown by comparisons between adult and postnatal brains and between housing conditions. Our study reveals the key morphological transitions of newborn granule neurons during their course of maturation.
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The process by which newly generated neurons in normal development are incorporated into the granular cell layer is well established and involves expression of specific markers and development of defined neuronal morphology.
“The process by which newly generated neurons in normal development are incorporated into the granular cell layer is well established and involves expression of specific markers and development of defined neuronal morphology24,26,34,35.”
From Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB (2021) · cites this paper as [35]
The Results section (‘Elaborate dendritic arborization of newborn cells within 3 weeks’; page not supplied) places newborn neurons in the granule cell layer, identifies neuronal-marker expression (NeuN), and describes their developing morphology. The Discussion defines four morphological maturation stages. But the Introduction says the timing and duration of these features were not clear, so calling the process ‘well established’ overstates the paper; its principal focus is adult mouse neurogenesis, although it also compares postnatal neurons. (LLM, conf=0.84)
Experimental — accuracy not yet measuredWithin 2 weeks of their generation, new neurons begin to take on morphological characteristics of mature granule cells, including a single dendritic tree extending toward the molecular layer and dendritic spines.
“Within 2 weeks of their generation, new neurons begin to take on the morphological characteristics of mature granule cells with a single dendritic tree extending toward the molecular layer and the formation of dendritic spines, primary sites of excitatory synapses (Zhao et al., 2006) (Figure 1A).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Zhao et al., 2006
Beginning less than 1 week after their generation, new granule cells extend mossy fiber axons through the hilus toward the CA3 and CA2 subregions.
“Beginning less than 1 week after their generation, new granule cells extend axons, known as mossy fibers, through the hilus toward the CA3 and CA2 subregions of the hippocampus (Llorens-Martín et al., 2015; Zhao et al., 2006).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Zhao et al., 2006
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- Authors
- Zhao, C., Teng, E. M., Summers, R. G., Ming, G.-L., & Gage, F. H.
- Affiliations
- Salk Institute for Biological Studies (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-01-04
- Volume
- 26
- Issue
- 1
- Pages
- 3-11
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674324
- OpenAlex
- W2002112050
- Cited by
- 1,257
- References
- 47
- Citations by year
- 2026: 27 · 2025: 37 · 2024: 37 · 2023: 35 · 2022: 26 · 2021: 70 · 2020: 68 · 2019: 59 · 2018: 61 · 2017: 83 · 2016: 84 · 2015: 78 · 2014: 81 · 2013: 84 · 2012: 69
- FWCI
- 19.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Milken Family Foundation
- American Epilepsy Society
- Epilepsy Foundation
- Epilepsy Society
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS052842, NS052842, R01NS050217, NS050217)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- adult neurogenesis, dentate gyrus, granule neurons, neuronal maturation, dendritic growth, axonal projections, dendritic spines, CA3, hippocampus, housing conditions, postnatal development
- MeSH terms
- Age Factors, Animals, Animals, Newborn, Axons, Cell Differentiation, Female, Hippocampus, Humans, Mice, Inbred C57BL, Neurons, Physical Conditioning, Animal, Dentate Gyrus, Dendritic Spines, Mice
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