Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures

Celine Dinocourt, Zdravko Petanjek, T. Freund, Yezekiel Ben-Ari, Monique Esclapez

Research output: Contribution to journalArticle

146 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)407-425
Number of pages19
JournalJournal of Comparative Neurology
Volume459
Issue number4
DOIs
Publication statusPublished - May 12 2003

Fingerprint

Pilocarpine
Pyramidal Cells
Interneurons
Dendrites
Hippocampus
Seizures
Parvalbumins
Somatostatin
Neurons
Hippocampal CA1 Region
Calbindins
GABAergic Neurons
Injections
Calcium-Binding Proteins
Axon Initial Segment
Presynaptic Terminals
Action Potentials
Axons
Cell Death
Messenger RNA

Keywords

  • Fluoro-jade B
  • GAD
  • Parvalbumin
  • Rat
  • Somatostatin
  • Temporal lobe epilepsy

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures. / Dinocourt, Celine; Petanjek, Zdravko; Freund, T.; Ben-Ari, Yezekiel; Esclapez, Monique.

In: Journal of Comparative Neurology, Vol. 459, No. 4, 12.05.2003, p. 407-425.

Research output: Contribution to journalArticle

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