Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures
Abstract
In the pilocarpine model of chronic limbic seizures, vulnerability of GABAergic interneurons to excitotoxic damage has been reported in the hippocampal CA1 region. However, little is known about the specific types of interneurons that degenerate in this region. In order to characterize these interneurons, we performed quantitative analyses of the different populations of GABAergic neurons labeled for their peptide or calcium-binding protein content. Our data demonstrate that the decrease in the number of GAD mRNA-containing neurons in the stratum oriens of CA1 in pilocarpine-treated rats involved two subpopulations of GABAergic interneurons: interneurons labeled for somatostatin only (O-LM and bistratified cells) and interneurons labeled for parvalbumin only (basket and axo-axonic cells). Stratum oriens interneurons labeled for somatostatin/calbindin or somatostatin/parvalbumin were preserved. The decrease in number of somatostatin- and parvalbumin-containing neurons was observed as early as 72 hours after the sustained seizures induced by pilocarpine injection. Many degenerating cell bodies in the stratum oriens and degenerating axon terminals in the stratum lacunosum-moleculare were observed at 1 and 2 weeks after injection. In addition, the synaptic coverage of the axon initial segment of CA1 pyramidal cells was significantly decreased in pilocarpine-treated animals. These results indicate that the loss of somatostatin-containing neurons corresponds preferentially to the degeneration of interneurons with an axon projecting to stratum lacunosum-moleculare (O-LM cells) and suggest that the death of these neurons is mainly responsible for the deficit of dendritic inhibition reported in this region. We demonstrate that the loss of parvalbumin-containing neurons corresponds to the death of axo-axonic cells, suggesting that perisomatic inhibition and mechanisms controlling action potential generation are also impaired in this model.
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NPD1 modulates the neuronal network in the CA1 during ictogenesis.
“suggesting that NPD1 modulates the neuronal network in the CA1 during ictogenesis, which is critical in kindling epileptogenesis [15] and in human and experimental TLE [48].”
From Hippocampal neuro-networks and dendritic spine perturbations in epileptogenesis are attenuated by neuroprotectin D1 (2015) · cites this paper as [48]
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- Authors
- Dinocourt, C., Petanjek, Z., Freund, T. F., Ben‐Ari, Y., & Esclapez, M.
- Affiliations
- Inserm (FR)
- Corresponding author
- Esclapez, Monique
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2003-04-03
- Volume
- 459
- Issue
- 4
- Pages
- 407-425
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2120205122
- Cited by
- 208
- References
- 82
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 11 · 2020: 4 · 2019: 9 · 2018: 9 · 2017: 9 · 2016: 4 · 2015: 7 · 2014: 12 · 2013: 12 · 2012: 13
- FWCI
- 7.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS30549)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- pilocarpine-induced seizures, hippocampal CA1, GABAergic interneurons, excitotoxicity, somatostatin interneurons, parvalbumin interneurons, axo-axonic cells, basket cells, stratum oriens, stratum lacunosum-moleculare, dendritic inhibition, axon initial segment, pyramidal neurons
- MeSH terms
- Animals, Axons, Dendrites, Hippocampus, Interneurons, Male, Pilocarpine, Seizures, Rats, Wistar, Pyramidal Cells, Rats
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