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Cited by 262Epilepsy research and treatmentNeural dynamics and brain functionNeuroscience and Neuropharmacology Research

Role of mossy fiber sprouting and mossy cell loss in hyperexcitability: a network model of the dentate gyrus incorporating cell types and axonal topography

Santhakumar, Vijayalakshmi, Aradi, Ildiko, Soltesz, Ivan·2005·Journal of Neurophysiology
DOI 10.1152/jn.00777.2004
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Abstract

Mossy cell loss and mossy fiber sprouting are two characteristic consequences of repeated seizures and head trauma. However, their precise contributions to the hyperexcitable state are not well understood. Because it is difficult, and frequently impossible, to independently examine using experimental techniques whether it is the loss of mossy cells or the sprouting of mossy fibers that leads to dentate hyperexcitability, we built a biophysically realistic and anatomically representative computational model of the dentate gyrus to examine this question. The 527-cell model, containing granule, mossy, basket, and hilar cells with axonal projections to the perforant-path termination zone, showed that even weak mossy fiber sprouting (10-15% of the strong sprouting observed in the pilocarpine model of epilepsy) resulted in the spread of seizure-like activity to the adjacent model hippocampal laminae after focal stimulation of the perforant path. The simulations also indicated that the spatially restricted, lamellar distribution of the sprouted mossy fiber contacts reported in in vivo studies was an important factor in sustaining seizure-like activity in the network. In contrast to the robust hyperexcitability-inducing effects of mossy fiber sprouting, removal of mossy cells resulted in decreased granule cell responses to perforant-path activation in agreement with recent experimental data. These results indicate the crucial role of mossy fiber sprouting even in situations where there is only relatively weak mossy fiber sprouting as is the case after moderate concussive experimental head injury.

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  • The previously built dentate gyrus model was used by several groups to study disparate topics including epilepsy, network mechanisms of inhibition and excitability, simulation optimization, and modeling software.

    “Previously, we built a dentate gyrus model to study epileptic network dynamics (Santhakumar et al., 2005; Morgan and Soltesz, 2008) that was then used by several groups to study disparate topics including epilepsy, network mechanisms of inhibition and excitability, simulation optimization, and modeling software”

    From Interneuronal mechanisms of hippocampal theta oscillations in a full-scale model of the rodent CA1 circuit (2016) · cites this paper as Santhakumar et al., 2005

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Authors
Santhakumar, V., Aradi, I., & Soltesz, I.
Affiliations
University of California, Los Angeles (US)
ORCID
Santhakumar, Vijayalakshmi
Venue
Journal of Neurophysiology
Publisher
American Physiological Society
Published
2005-01
Volume
93
Issue
1
Pages
437-453
ISSN
  • 0022-3077 (ISSN-L)
  • 1522-1598
DOI
10.1152/jn.00777.2004
OpenAlex
W2154731415
Cited by
262
References
96
Citations by year
2026: 4 · 2025: 13 · 2024: 7 · 2023: 11 · 2022: 17 · 2021: 12 · 2020: 5 · 2019: 13 · 2018: 14 · 2017: 13 · 2016: 16 · 2015: 14 · 2014: 10 · 2013: 18 · 2012: 18
FWCI
4.98
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurophysiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (NS-35915)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
mossy fiber sprouting, computational network model, granule cells, perforant path, seizure-like activity, head trauma, concussion, basket cells
MeSH terms
Animals, Cell Count, Cell Survival, Computer Simulation, Dose-Response Relationship, Radiation, Electric Stimulation, Membrane Potentials, Models, Neurological, Neural Conduction, Neural Inhibition, Synaptic Transmission, Neurons, Seizures, Time Factors, Neural Networks, Computer, Dentate Gyrus, Mossy Fibers, Hippocampal

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