Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus - PubMed (original) (raw)
Comparative Study
Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus
Chunmei Zhao et al. J Neurosci. 2006.
Abstract
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.
Figures
Figure 1.
The morphological development of neurons born in the adult mouse brain. Dividing cells in the dentate gyrus of 7- to 10-week-old C57BL/6 mice were labeled with GFP through retrovirus-mediated gene transduction. Mice were killed at different time points as indicated. Images are oriented with the molecular layer on the upside. a, Cells at 3 dpi. b, Cells at 7 dpi. c, Cells at 10, 14, 21, 28, and 56 dpi, and also 14 mpi. Scale bars, 50 μm. DAPI is red; GFP is green.
Figure 2.
The initiation of spine genesis in newly generated granule neurons. a, Examples of dendritic segments from mouse brains taken at 14, 21, and 28 dpi. Scale bar, 5 μm. b, Examples of dendritic segments at 15, 16, and 17 dpi. Scale bar, 5 μm. c, Examples of dendritic segments of neurons born at P10. Spines start to grow before 12 dpi (middle panel). Scale bar, 5 μm. d, Representative images of more mature-looking cells at 12 dpi. Scale bar, 50μm. e, Quantification of dendritic length of cells born in the adult brain at 12 and 16 dpi, as well as cells born at P10 at 12 dpi. f, Quantification of branching points. Data are presented as mean ± SEM in e and f.
Figure 3.
Axonal growth in newborn granule neurons. Sections of similar levels in the anterior–posterior axis were imaged for axonal growth in the adult (a–h). Arrows indicate the end of the fibers. DAPI is red; GFP is green. Scale bar, 100 μm. GFP signal in c_–_h was enhanced by GFP antibody staining. a, The standard hippocampal section used for all time points. The square indicates the CA3 area imaged in b and d–h. b, Axonal fibers at 56 dpi were used as reference. c, The labeling at 10 dpi in the dentate gyrus, showing that the lack of GFP in d is not caused by a lack of labeling. Thin fibers are clearly seen in the hilus (arrow). d–h, Axonal fibers in the CA3 area at 10, 11, 12, 14, and 16 dpi. i, Axonal growth of neurons labeled at P10.
Figure 4.
The maturation of granule neurons born in the adult mouse brain: dendritic spine analyses. a, Representative images of dendritic segments from newborn neurons at 21, 28, 42, 56, and 126 d after viral infection. b, Quantification of total protrusion density. Blue indicates control; purple indicates running. The density of protrusions is expressed as the number of protrusions per micrometer of dendritic length. c, Quantification of mushroom spine density. Mushroom spines were identified if the estimated surface area (=π × _D_major × _D_minor/4) was ≥ 0.4μm2. The density of mushroom spines is expressed as the total number of mushroom spines per micrometer of dendritic length. d, An example of time-lapse series of a dendritic segment for spine motility analysis. The arrow indicates partial retractions of a spine over the time series. e, Quantification of spine motility. Data for b, c, and e are presented as mean ± SEM. The asterisks indicate where significant differences were seen between control and running mice (p < 0.01). Scale bars, 2μm.
Figure 5.
Representative images of GFP labeling in control and running mice at 56 dpi.
Figure 6.
Summary of granule neuron maturation in the adult mouse hippocampus. a, Granule neuron maturation was separated into four stages. Stage A covers the initial events after the cell exits the cell cycle, including differentiation, polarization, migration, and the initial neurite outgrowth. Stage B involves dendritic and axonal growth. B1 and B2 are separated at the time when axon fibers first enter the CA3 area. The initiation of spine growth marks the beginning of stage C, and this stage covers the later dendritic and axonal growth. Stage D starts shortly after spine formation during stage C and continues for several months. DG, Dentate gyrus; HF, hippocampal fissure. b, Temporal map of morphogenetic events during the maturation of newborn granule neurons. The arrowheads indicate key events during early morphogenesis: the migration of axon fibers into the CA3 area and the initiation of spine genesis.
References
- Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124: 319–335. - PubMed
- Ambrogini P, Lattanzi D, Ciuffoli S, Agostini D, Bertini L, Stocchi V, Santi S, Cuppini R (2004) Morpho-functional characterization of neuronal cells at different stages of maturation in granule cell layer of adult rat dentate gyrus. Brain Res 1017: 21–31. - PubMed
- Ben-Ari Y (2001) Developing networks play a similar melody. Trends Neurosci 24: 353–360. - PubMed
- Bonhoeffer T, Yuste R (2002) Spine motility: phenomenology, mechanisms, and function. Neuron 35: 1019–1027. - PubMed
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