Adult neurogenesis modifies excitability of the dentate gyrus
Open accessAbstract
Adult-born dentate granule neurons contribute to memory encoding functions of the dentate gyrus (DG) such as pattern separation. However, local circuit-mechanisms by which adult-born neurons partake in this process are poorly understood. Computational, neuroanatomical and electrophysiological studies suggest that sparseness of activation in the granule cell layer (GCL) is conducive for pattern separation. A sparse coding scheme is thought to facilitate the distribution of similar entorhinal inputs across the GCL to decorrelate overlapping representations and minimize interference. Here we used fast voltage-sensitive dye (VSD) imaging combined with laser photostimulation and electrical stimulation to examine how selectively increasing adult DG neurogenesis influences local circuit activity and excitability. We show that DG of mice with more adult-born neurons exhibits decreased strength of neuronal activation and more restricted excitation spread in GCL while maintaining effective output to CA3c. Conversely, blockade of adult hippocampal neurogenesis changed excitability of the DG in the opposite direction. Analysis of GABAergic inhibition onto mature dentate granule neurons in the DG of mice with more adult-born neurons shows a modest readjustment of perisomatic inhibitory synaptic gain without changes in overall inhibitory tone, presynaptic properties or GABAergic innervation pattern. Retroviral labeling of connectivity in mice with more adult-born neurons showed increased number of excitatory synaptic contacts of adult-born neurons onto hilar interneurons. Together, these studies demonstrate that adult hippocampal neurogenesis modifies excitability of mature dentate granule neurons and that this non-cell autonomous effect may be mediated by local circuit mechanisms such as excitatory drive onto hilar interneurons. Modulation of DG excitability by adult-born dentate granule neurons may enhance sparse coding in the GCL to influence pattern separation.
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Changes in the number of new neurons, which alter the overall excitability of the hippocampus, may then regulate the expression of PNNs at postsynaptic sites.
“one possibility is that changes in the number of new neurons, which alter the overall excitability of the hippocampus (Ikrar et al., 2013), may then regulate the expression of PNNs at postsynaptic sites.”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Ikrar et al., 2013
The process of neurogenesis modifies the excitation of hippocampal neurons.
“It has been extensively demonstrated that the process of neurogenesis modifies the excitation of hippocampal neurons (Ikrar et al., 2013).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Ikrar et al., 2013
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- Authors
- Ikrar, T., Guo, N., He, K., Besnard, A., Levinson, S., Hill, A., Lee, H.-K., Hen, R., Xu, X., & Sahay, A.
- Affiliations
- University of California, Irvine (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Columbia University (US)
- Corresponding author
- Xu, Xiangmin
- Sahay, Amar
- Venue
- Frontiers in Neural Circuits
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 7
- Pages
- 204-204
- ISSN
- 1662-5110 (ISSN-L)
- PMC
- PMC3872742
- OpenAlex
- W2011230199
- Cited by
- 192
- References
- 72
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 12 · 2023: 12 · 2022: 14 · 2021: 15 · 2020: 24 · 2019: 22 · 2018: 13 · 2017: 15 · 2016: 17 · 2015: 22 · 2014: 8
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neural Circuits (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Columbia Academic Commons (Columbia University)
- Funders
- Ellison Medical Foundation
- Hope for Depression Research Foundation
- National Alliance for Research on Schizophrenia and Depression
- Philippe Foundation
- Fondation Bettencourt Schueller
- Servier
- H. Lundbeck A/S
- National Institutes of Health
- National Institute of Mental Health (R00MH086615, R01MH068542)
- National Eye Institute (R01EY014882)
- National Institute of Neurological Disorders and Stroke (R01NS078434)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007430)
- 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, dentate gyrus granule cells, neuronal excitability, pattern separation, sparse coding, GABAergic inhibition, hilar interneurons, non-cell-autonomous effects, voltage-sensitive dye imaging
- MeSH terms
- Animals, Neural Inhibition, Neuronal Plasticity, Neurons, Synapses, Dentate Gyrus, Mice, Inhibitory Postsynaptic Potentials, Miniature Postsynaptic Potentials, Neurogenesis
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