Neuroethologically delineated differences in the seizure behavior of Synapsin 1 and Synapsin 2 knock-out mice

Etholm, Lars; Bahonjic, Elma; Walaas, Sven Ivar; Kao, Hung-Teh; Heggelund, Paul

doi:10.1016/j.eplepsyres.2011.12.004

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Volume 99, Issue 3 , Pages 252-259, May 2012

Neuroethologically delineated differences in the seizure behavior of Synapsin 1 and Synapsin 2 knock-out mice

Lars Etholm
- Section of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital - Rikshospitalet, Oslo, Norway
- Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, Oslo, Norway
- Corresponding author at: Section of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital - Rikshospitalet, Box-4956 Nydalen, 0424 Oslo, Norway. Tel.: +47 23 07 00 00; fax: +47 23 07 04 90.
Elma Bahonjic
- Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, Oslo, Norway
Sven Ivar Walaas
- Institute of Basic Medical Sciences, Department of Biochemistry, University of Oslo, Oslo, Norway
Hung-Teh Kao
- Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA
Paul Heggelund
- Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, Oslo, Norway

Received 4 October 2011; received in revised form 25 November 2011; accepted 1 December 2011. published online 11 January 2012.

Summary

The highly homologous nerve terminal phosphoproteins synapsin I and synapsin II have been linked to the pathogenesis of epilepsy through associations between synapsin gene mutations and epileptic disease in humans and to the observation of handling induced seizures in mice genetically depleted of one or both of these proteins. Whereas seizure behavior in mice lacking both synapsin I and synapsin II is well characterized, the seizure behavior in mice lacking either is less well studied. Through so called neuroethologically based analyses of fully established seizure behavior in Synapsin 1 and 2 knock-out mice (Syn1KO and Syn2KO mice) aged 4 1/2 months, this study reveals significant differences in the seizure behavior of the two genotypes: whereas Syn1KO mice show both partial and generalized forebrain seizure activity, Syn2KO mice show only fully generalized forebrain seizures. Analysis of seizure behavior at earlier stages shows that the mature seizure pattern in Syn2KO mice establishes rapidly from the age of ∼2 months, when Syn1KO partial seizures are rare, and Syn1KO generalized seizures are almost absent. The specific behavioral phenotypes of the two strains suggest that the slight differences in structure, function and expression of these highly related proteins could be important factors during seizure generating neural activity.

Abbreviations: EMT, emprostotonus, EPT, epistotonus, MYO, isolated myoclonus, PPL, post provocational latency, ROT, retraction associated orofacial twitching, RUN, running fit, Syn, synapsin, Syn1, Synapsin 1 gene, Syn2, Synapsin 2 gene, Syn3, Synapsin 3 gene, SynKO, synapsin knock-out, Syn1KO, Synapsin 1 knock-out, Syn2KO, Synapsin 2 knock-out, Syn3KO, Synapsin 3 knock-out, SynDKO, Synapsin 1/2 double knock-out, SynTKO, Synapsin 1/2/3 triple knock-out, Syn I, synapsin I protein, Syn II, synapsin II protein, Syn III, synapsin III protein