Distinct Morphological Stages of Dentate Granule Neuron Maturation in the Adult Mouse Hippocampus

By Chunmei Zhao, E. Teng, R. Summers, Guo-li Ming, Fred H. Gage. 2006

1,283 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology

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Citations in the corpus

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “DCX + neuroblasts in the adult SVZ can be converted to an oligodendrocyte fate upon demyelination of the corpus callosum (Jablonska et al., 2010) Stage Markers Synaptic integration Critical period Calbindin 1 2 3 4 5 Radial glia -like (Type I cell) Intermediate progenitor cell (IP) Neuroblast Mature”
New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? (2010, background): “The newly born DGCs bear little resemblance to their mature counterparts and must undergo a lengthy process of morphological and physiological maturatio”
Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. (2009, background): “Spine formation of newly born neurons starts around 3 weeks after cell division (Toni et al., 2007; Zhao et al., 2006 ).”
Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior. (2016, positive): “Dendritic spines form at 16 days in a process that appears to be controlled by local astrocytes (Sultan et al., 2015; Zhao et al., 2006), but the first glutamatergic inputs into newborn neurons seem to originate as early as 10 days from hilar mossy cells (Deshpande et al.”
Adult neurogenesis and functional plasticity in neuronal circuits (2006, background): “As they differentiate, the dendrites of newborn dentate gyrus cells become progressively more complex and extend deeper into the molecular cell laye”
Seizure-Associated, Aberrant Neurogenesis in Adult Rats Characterized with Retrovirus-Mediated Cell Labeling (2007, methodology): “Retroviruses were produced as described previously (Zhao et al., 2006).”
Temporal Discontiguity Is neither Necessary nor Sufficient for Learning-Induced Effects on Adult Neurogenesis (2006, background): “Adult neurogenesis is a fundamental form of plasticity because it leads to the growth of new dendrites, axons, and synapses (Hastings and Gould, 1999; van Praag et al., 2002; Zhao et al., 2006).”
Experience-dependent structural synaptic plasticity in the mammalian brain (2009, background): “Apart from the growth of dendritic trees of adult-born neuron”
Neurogenesis in the Adult Hippocampus. (2015, background): “Axon outgrowth is initiated before synaptic contacts on the dendritic tree are made (Zhao et al. 2006).”
Neurogenesis and Exercise: Past and Future Directions (2008, background): “Specifically, the density of mushroom spines is enhanced and spine motility is decreased during development of new neurons in the adult brain, even though the total number of dendritic protrusions does not change (Zhao et al. 2006).”
Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer’s Disease (2009, positive): “Adult-Born GCs in hAPP-J20 Mice Display Impaired Maturation and Functional Responses The dendritic growth of wild-type adult-born GCs starts to plateau at about 28 days after their birth (Zhao et al., 2006).”
Dopaminergic Modulation of Cortical Inputs during Maturation of Adult-born Dentate Granule Cells (2011, methodology): “, 2005), and 8 weeks to display mature morphology (Zhao et al., 2006).”
Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis (2010, background): “, 2006), but the early survival in such experiments has not been reported, because the expression of the genes delivered by viral vectors generally takes several days (Zhao et al., 2006).”
SANDI: A compartment-based model for non-invasive apparent soma and neurite imaging by diffusion MRI (2019, positive): “…to 3 ms/ μ m 2 ) and that the high b value regime can be used to increase sensitivity to geometrical restrictions of typical neural soma size ranging from a few microns (e.g. for microglia and glia) to a few tens of microns (e.g. for big neurons) (Zhao et al., 2006; Diaz-Cintra et al., 2004) (Figs.”
Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior (2008, background): “Consistent with findings in wild-type mice (10), total spine density was high and few spines with mushroom morphology were detected at this stage of development.”
Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons. (2007, methodology): “Dendritic spine density is a morphological indicator of neuronal maturation in hippocampal granule cells, and reduced spine density is correlated with impaired maturation of DG neurons (Zhao et al., 2006).”
Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain (2008, methodology): “Sections were imaged with confocal microscopy at 1- m intervals, and projection images were used for analysis of axonal growth as previously described (8).”