Kainic acid-induced mossy fiber sprouting and synapse formation in the dentate gyrus of rats

H. J. Wenzel, C. S. Woolley, C. A. Robbins, Philip A Schwartzkroin

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

In the kainic acid (KA) model of temporal lobe epilepsy, mossy fibers (MFs) are thought to establish recurrent excitatory synaptic contacts onto granule cells. This hypothesis was tested by intracellular labeling of granule cells with biocytin and identifying their synaptic contacts in the dentate molecular layer with electron microscopic (EM) techniques. Twenty-three granule cells from KA-treated animals and 14 granule cells from control rats were examined 2 to 4 months following KA at the light microscopic (LM) level; four cells showing MF sprouting were further characterized at the EM level. Timm staining revealed a time-dependent growth of aberrant MFs into the dentate inner molecular layer. The degree of sprouting was generally (but not invariably) correlated with the severity and frequency of seizures. LM examination of individual biocytin-labeled MF axon collaterals revealed enhanced collateralization and significantly increased numbers of synaptic MF boutons in the hilus compared to controls, as well as aberrant MF growth into the granule cell and molecular layers. EM examination of serially reconstructed, biocytin-labeled MF collaterals in the molecular layer revealed MF boutons that form asymmetrical synapses with dendritic shafts and spines of granule cells, including likely autaptic contacts on parent dendrites of the biocytin-labeled granule cell. These results constitute ultrastructural evidence for newly formed excitatory recurrent circuits, which might provide a structural basis for enhanced excitation and epileptogenesis in the hippocampus of KA-treated rats. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)244-260
Number of pages17
JournalHippocampus
Volume10
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Kainic Acid
Dentate Gyrus
Synapses
Electrons
Light
Dendritic Spines
Temporal Lobe Epilepsy
Growth
Dendrites
Axons
Hippocampus
Seizures
Staining and Labeling
biocytin

Keywords

  • Biocytin
  • Electron microscopy
  • Epilepsy
  • Synaptic reorganization

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kainic acid-induced mossy fiber sprouting and synapse formation in the dentate gyrus of rats. / Wenzel, H. J.; Woolley, C. S.; Robbins, C. A.; Schwartzkroin, Philip A.

In: Hippocampus, Vol. 10, No. 3, 2000, p. 244-260.

Research output: Contribution to journalArticle

Wenzel, H. J. ; Woolley, C. S. ; Robbins, C. A. ; Schwartzkroin, Philip A. / Kainic acid-induced mossy fiber sprouting and synapse formation in the dentate gyrus of rats. In: Hippocampus. 2000 ; Vol. 10, No. 3. pp. 244-260.
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