Artikel
The presynaptic active zone protein RIM1α controls epileptogenesis following status epilepticus
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Veröffentlicht: | 11. September 2012 |
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In order 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 multi-domain 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.
Here, we addressed the role of RIM1α in aberrant cellular plasticity and structural reorganization after a transient brain insult, by subjecting mice deficient in RIM1α to pharmacologically induced status epilepticus (SE). After a latent period, RIM1α-deficient mice (RIM1α-/-) develop spontaneous seizures of dramatically increased frequency compared to controls. Intriguingly, they show a selective hilar damage pattern, i.e. endfolium sclerosis as well as less severe astrogliosis and attenuated mossy fiber sprouting. Furthermore, there was an increase in paired-pulse facilitation in the CA1 region of the hippocampus in wildtype mice (RIM1α+/+) after SE 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. 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.
This data supports a direct regulation of RIM1α during epileptogenesis and therefore improves a novel molecular target of seizure induced maladaptive plasticity.
Acknowledgements: This work was supported by grants from the DFG (EmmyNoether Program SS, SFB/TR3 HB, SS and AB), the BMBF (NGFNplus HB, SS and AB, Unabhängige Forschergruppen in den Neurowissenschaften SS), Neuron ERANET 'EpiNet' to HB, Euroepinomics (AB), Else Kröner Fresenius Foundation (AB), German Israeli Foundation (AB) and BONFOR (SS, HB and AB).