Maturation dynamics of the axon initial segment (AIS) of newborn dentate granule cells in young adult C57BL/6J mice
Open accessAbstract
Newborn dentate granule cells (DGCs) are generated in the hippocampal dentate gyrus (DG) of rodents through a process called adult hippocampal neurogenesis, which is subjected to tight intrinsic and extrinsic regulation. The use of retroviruses encoding fluorescent proteins has allowed the characterization of the maturation dynamics of newborn DGCs, including their morphological development and the establishment and maturation of their afferent and efferent synaptic connections. However, the study of a crucial cellular compartment of these cells, namely, the axon initial segment (AIS), has remained unexplored to date. The AIS is not only the site of action potential initiation, but it also has a unique molecular identity that makes it one of the master regulators of neural plasticity and excitability. Here we examined the dynamics of AIS formation in newborn DGCs of young female adult C57BL/6J mice in vivo. Our data reveal notable changes in AIS length and thickness throughout cell maturation under physiological conditions and show that the most remarkable structural changes coincide with periods of intense morphological and functional remodeling. Moreover, we demonstrate that AIS development can be modulated extrinsically by both neuroprotective (environmental enrichment) and detrimental (lipopolysaccharide from Escherichia coli) stimuli. SIGNIFICANCE STATEMENT The hippocampal dentate gyrus (DG) of rodents generates newborn dentate granule cells (DGCs) throughout life. This process, named adult hippocampal neurogenesis, confers a unique degree of plasticity to the hippocampal circuit, and it is crucial for learning and memory. Here we studied, for the first time, the formation of a key cellular compartment of newborn DGCs, namely, the axon initial segment (AIS) in vivo. Our data reveal remarkable AIS structural remodeling throughout the maturation of these cells under physiological conditions. Moreover, AIS development can be modulated extrinsically by both neuroprotective (environmental enrichment) and detrimental (lipopolysaccharide from Escherichia coli) stimuli.
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The length of the axonal initial segment (AIS) is related to neuronal maturation and to some pathologic conditions.
“The axonal initial segment (AIS) is also a dynamic structure, the length of which is related to neuronal maturation (Gutzmann et al., 2014;Bolós et al., 2019) and also to some pathologic conditions (Kuba et al., 2010;Baalman et al., 2013;Harty et al., 2013).”
From Perineuronal Nets Regulate the Inhibitory Perisomatic Input onto Parvalbumin Interneurons and γ Activity in the Prefrontal Cortex (2020) · cites this paper as Bolós et al., 2019
Increase in AIS length is related to the maturation of other neuronal types.
“Since the increase in AIS length has been previously related to the maturation of other neuronal types (Sammons et al., 2018;Bolós et al., 2019)”
From Perineuronal Nets Regulate the Inhibitory Perisomatic Input onto Parvalbumin Interneurons and γ Activity in the Prefrontal Cortex (2020) · cites this paper as Bolós et al., 2019
Cites
Stimulus-transcription coupling in neurons: role of cellular immediate-early genes
Morgan, J. I., & Curran, T. (1989) · Trends in Neurosciences · doi:10.1016/0166-2236(89)90096-9 · Cited by 969 · cited 2× · see citing works
“EE increases the activation of newborn DGCs To further characterize the mechanisms through which EE accelerated the maturation of newborn DGCs, we next studied the expression of cfos, an early immediate gene that shows nuclear localization under conditions of neuronal activation (Morgan and Curran, 1989), in the GCL o…”
BackgroundAction potential generation requires a high sodium channel density in the axon initial segment
Kole, M. H. P., Ilschner, S. U., Kampa, B. M., Williams, S. R., Ruben, P. C., & Stuart, G. J. (2008) · Nature Neuroscience · doi:10.1038/nn2040 · Cited by 703 · see citing works
Neurofascin assembles a specialized extracellular matrix at the axon initial segment
Hedstrom, K. L., Xu, X., Ogawa, Y., Frischknecht, R., Seidenbecher, C. I., Shrager, P., & Rasband, M. N. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200705119 · Cited by 268 · see citing works
Llorens-Martín, M., Jurado-Arjona, J., Bolós, M., Pallas-Bazarra, N., & Ávila, J. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.12.019 · Cited by 43 · see citing works
Acute neuroinflammation induces AIS structural plasticity in a NOX2-dependent manner
Benusa, S. D., George, N. M., Sword, B. A., DeVries, G. H., & Dupree, J. L. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0889-3 · Cited by 31 · see citing works
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Adult neurogenesis, glia, and the extracellular matrix
Cope, E. C., & Gould, E. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.03.023 · Cited by 236 · see citing works
Carceller, H., Guirado, R., Ripolles-Campos, E., Teruel-Marti, V., & Nacher, J. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.0291-20.2020 · Cited by 112 · see citing works
- Authors
- Bolós, M., Terreros-Roncal, J., Perea, Jr., Pallas-Bazarra, N., Ávila, J., & Llorens-Martín, M.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2019-01-16
- Volume
- 39
- Issue
- 9
- Pages
- 2253-18
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6391570
- OpenAlex
- W2910265782
- Cited by
- 14
- References
- 5
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 1
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion)
- Hispana (publishedVersion)
- Biblos-e Archivo (Universidad Autónoma de Madrid) (submittedVersion, public-domain)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Centro de Biología Molecular Severo Ochoa
- Ministerio de Economía y Competitividad (SAF-2017-82185-R, RYC-2015-171899)
- 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
- axon initial segment, dentate gyrus granule cells, adult hippocampal neurogenesis, cell maturation, dentate gyrus, environmental enrichment, lipopolysaccharide, neuroinflammation, neuronal excitability, in vivo imaging
- MeSH terms
- Action Potentials, Animals, Axons, Female, Mice, Inbred C57BL, Dentate Gyrus, Mice, Neurogenesis
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