title: The presynaptic active zone protein RIM1α controls epileptogenesis following status epilepticus.
abstract: To ensure operation of synaptic transmission within an appropriate dynamic range, neurons have evolved mechanisms of activity-dependent plasticity, including changes in presynaptic efficacy. The multidomain protein RIM1α is an integral component of the cytomatrix at the presynaptic active zone and has emerged as key mediator of presynaptically expressed forms of synaptic plasticity. We have therefore addressed the role of RIM1α in aberrant cellular plasticity and structural reorganization after an episode of synchronous neuronal activity pharmacologically induced in vivo [status epilepticus (SE)]. Post-SE, all animals developed spontaneous seizure events, but their frequency was dramatically increased in RIM1α-deficient mice (RIM1α(-/-)). We found that in wild-type mice (RIM1α(+/+)) SE caused an increase in paired-pulse facilitation in the CA1 region of the hippocampus to the level observed in RIM1α(-/-) mice before SE. In contrast, this form of short-term plasticity was not further enhanced in RIM1α-deficient mice after SE. Intriguingly, RIM1α(-/-) mice showed a unique pattern of selective hilar cell loss (i.e., endfolium sclerosis), which so far has not been observed in a genetic epilepsy animal model, as well as less severe astrogliosis and attenuated mossy fiber sprouting. These findings indicate that the decrease in release probability and altered short- and long-term plasticity as present in RIM1α(-/-) mice result in the formation of a hyperexcitable network but act in part neuroprotectively with regard to neuropathological alterations associated with epileptogenesis. In summary, our results suggest that presynaptic plasticity and proper function of RIM1α play an important part in a neuron's adaptive response to aberrant electrical activity.
authors.affiliation: Department of Neuropathology, University of Bonn, 53105 Bonn, Germany.
authors.forename: Julika
authors.initials: J
authors.lastname: Pitsch
authors.forename: Thoralf
authors.initials: T
authors.lastname: Opitz
authors.forename: Verena
authors.initials: V
authors.lastname: Borm
authors.forename: Anne
authors.initials: A
authors.lastname: Woitecki
authors.forename: Matthäus
authors.initials: M
authors.lastname: Staniek
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D013226:Status Epilepticus / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*
chemical_list: C491490:Rims1 protein, mouse; D019204:GTP-Binding Proteins