title: Plasticity of GABA(B) receptor-mediated heterosynaptic interactions at mossy fibers after status epilepticus.
abstract: Several neurotransmitters, including GABA acting at presynaptic GABA(B) receptors, modulate glutamate release at synapses between hippocampal mossy fibers and CA3 pyramidal neurons. This phenomenon gates excitation of the hippocampus and may therefore prevent limbic seizure propagation. Here we report that status epilepticus, triggered by either perforant path stimulation or pilocarpine administration, was followed 24 hr later by a loss of GABA(B) receptor-mediated heterosynaptic depression among populations of mossy fibers. This was accompanied by a decrease in the sensitivity of mossy fiber transmission to the exogenous GABA(B) receptor agonist baclofen. Autoradiography revealed a reduction in GABA(B) receptor binding in the stratum lucidum after status epilepticus. Failure of GABA(B) receptor-mediated modulation of mossy fiber transmission at mossy fibers may contribute to the development of spontaneous seizures after status epilepticus.
authors.affiliation: Institute of Neurology, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Chandler
authors.forename: Alessandra P
authors.initials: AP
authors.lastname: Princivalle
authors.forename: Ruth
authors.initials: R
authors.lastname: Fabian-Fine
authors.forename: Norman G
authors.initials: NG
authors.lastname: Bowery
authors.forename: Dimitri M
authors.initials: DM
authors.lastname: Kullmann
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Walker
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology*; D009433:Neural Inhibition; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D013226:Status Epilepticus / Q000378:metabolism / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism
chemical_list: D018755:GABA Agonists; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; D005680:gamma-Aminobutyric Acid; D001418:Baclofen