| First Author | Pitsch J | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 36 | Pages | 12384-95 |
| PubMed ID | 22956829 | Mgi Jnum | J:187680 |
| Mgi Id | MGI:5437781 | Doi | 10.1523/JNEUROSCI.0223-12.2012 |
| Citation | Pitsch J, et al. (2012) The Presynaptic Active Zone Protein RIM1alpha Controls Epileptogenesis following Status Epilepticus. J Neurosci 32(36):12384-95 |
| abstractText | 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 RIM1alpha 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 RIM1alpha 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 RIM1alpha-deficient mice (RIM1alpha(-/-)). We found that in wild-type mice (RIM1alpha(+/+)) SE caused an increase in paired-pulse facilitation in the CA1 region of the hippocampus to the level observed in RIM1alpha(-/-) mice before SE. In contrast, this form of short-term plasticity was not further enhanced in RIM1alpha-deficient mice after SE. Intriguingly, RIM1alpha(-/-) 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 RIM1alpha(-/-) 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 RIM1alpha play an important part in a neuron's adaptive response to aberrant electrical activity. |
