title: Altered neurotransmitter release, vesicle recycling and presynaptic structure in the pilocarpine model of temporal lobe epilepsy.
abstract: In searching for persistent seizure-induced alterations in brain function that might be causally related to epilepsy, presynaptic transmitter release has relatively been neglected. To measure directly the long-term effects of pilocarpine-induced status epilepticus on vesicular release and recycling in hippocampal mossy fibre presynaptic boutons, we used (i) two-photon imaging of FM1-43 vesicular release in rat hippocampal slices; and (ii) transgenic mice expressing the genetically encoded pH-sensitive fluorescent reporter synaptopHluorin preferentially at glutamatergic synapses. In this study we found that, 1-2 months after pilocarpine-induced status epilepticus, there were significant increases in mossy fibre bouton size, faster rates of action potential-driven vesicular release and endocytosis. We also analysed the ultrastructure of rat mossy fibre boutons using transmission electron microscopy. Pilocarpine-induced status epilepticus led to a significant increase in the number of release sites, active zone length, postsynaptic density area and number of vesicles in the readily releasable and recycling pools, all correlated with increased release probability. Our data show that presynaptic release machinery is persistently altered in structure and function by status epilepticus, which could contribute to the development of the chronic epileptic state and may represent a potential new target for antiepileptic therapies.
authors.affiliation: Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Chirag
authors.initials: C
authors.lastname: Upreti
authors.forename: Rafael
authors.initials: R
authors.lastname: Otero
authors.forename: Carlos
authors.initials: C
authors.lastname: Partida
authors.forename: Frank
authors.initials: F
authors.lastname: Skinner
authors.forename: Ravi
authors.initials: R
authors.lastname: Thakker
authors.forename: Luis F
authors.initials: LF
authors.lastname: Pacheco
authors.forename: Zhen-yu
authors.initials: ZY
authors.lastname: Zhou
authors.forename: Giorgi
authors.initials: G
authors.lastname: Maglakelidze
authors.forename: Jana
authors.initials: J
authors.lastname: Velíšková
authors.forename: Libor
authors.initials: L
authors.lastname: Velíšek
authors.forename: Dwight
authors.initials: D
authors.lastname: Romanovicz
authors.forename: Theresa
authors.initials: T
authors.lastname: Jones
authors.forename: Patric K
authors.initials: PK
authors.lastname: Stanton
authors.forename: Emilio R
authors.initials: ER
authors.lastname: Garrido-Sanabria
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D003292:Convulsants; D018891:Dentate Gyrus / Q000473:pathology; D055724:Electrophysiological Phenomena; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000473:pathology; D009473:Neuronal Plasticity; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010862:Pilocarpine; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017661:Receptors, Presynaptic / Q000378:metabolism*; D013226:Status Epilepticus / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000473:pathology; D016707:Tissue Fixation
chemical_list: D003292:Convulsants; C073804:FM1 43; D005456:Fluorescent Dyes; D018377:Neurotransmitter Agents; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D017661:Receptors, Presynaptic; D010862:Pilocarpine