title: Replacement of Asymmetric Synaptic Profiles in the Molecular Layer of Dentate Gyrus Following Cycloheximide in the Pilocarpine Model in Rats.
abstract: Mossy fiber sprouting is among the best-studied forms of post-lesional synaptic plasticity and is regarded by many as contributory to seizures in both humans and animal models of epilepsy. It is not known whether mossy fiber sprouting increases the number of synapses in the molecular layer or merely replaces lost contacts. Using the pilocarpine (Pilo) model of status epilepticus to induce mossy fiber sprouting, and cycloheximide (CHX) to block this sprouting, we evaluated at the ultrastructural level the number and type of asymmetric synaptic contacts in the molecular layer of the dentate gyrus. As expected, whereas Pilo-treated rats had dense silver grain deposits in the inner molecular layer (IML) (reflecting mossy fiber sprouting), pilocarpine + cycloheximide (CHX + Pilo)-treated animals did not differ from controls. Both groups of treated rats (Pilo group and CHX + Pilo group) had reduced density of asymmetric synaptic profiles (putative excitatory synaptic contacts), which was greater for CHX-treated animals. For both treated groups, the loss of excitatory synaptic contacts was even greater in the outer molecular layer than in the best-studied IML (in which mossy fiber sprouting occurs). These results indicate that mossy fiber sprouting tends to replace lost synaptic contacts rather than increase the absolute number of contacts. We speculate that the overall result is more consistent with restored rather than with increased excitability.
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Bittencourt
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Luciene
authors.initials: L
authors.lastname: Covolan
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital , Toronto, ON , Canada.
authors.forename: Clement
authors.initials: C
authors.lastname: Hamani
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Longo
authors.affiliation: Electron Microscopy Center, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Flávio P
authors.initials: FP
authors.lastname: Faria
authors.affiliation: Electron Microscopy Center, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Edna
authors.initials: E
authors.lastname: Freymuller
authors.affiliation: Department of Anatomy, Centre for Molecular Biology and Neuroscience, University of Oslo , Oslo , Norway.
authors.forename: Ole P
authors.initials: OP
authors.lastname: Ottersen
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Mello
keywords: asymmetric synaptic profiles; cycloheximide; epilepsy; mossy fiber sprouting; synaptic plasticity