Abstracts

Rationale: The synapsins constitute a phosphoprotein family located in nerve terminals where they are involved in synaptic vesicle trafficking. Synapsin I/II double knock-out mice (DKO-mice) develop sensory provoked seizures previously described as grand mal like attacks with arched backs, inability to stay upright and post-seizure grooming. Mice deficient in synapsin show some disability on learning tasks, but neither ataxia nor any gross anatomical brain deformities. At a cellular level, the mice appear functionally normal except for changes in some aspects of short term plasticity. This study aims at clarifying the components of seizure activity in the DKO-mouse, and assess its value for further epilepsy related studies.Methods: Seizures provoked by complex sensory stimulation in freely moving DKO-mice were studied through simultaneous behavioral observations (video recordings), and electrophysiological registrations of cortical EEG and thalamic field potentials.Results: Seizure activity in DKO-mice include pronounced orofacial, forelimb and combined orofacial/forelimb myoclonies both in isolation and in combination with aforementioned 'grand mal like' seizures. Myoclonic phases occur alongside low-frequency spike-wave EEG complexes in synchrony with large-amplitude thalamic field potentials.Conclusions: The seizures of DKO-mice show a greater variety than previously reported. The occurence of synchronous cortical and thalamic seizure activity during myoclonies is suggesting a role for the thalamocortical circuitry in the myoclonic pathophysiology in DKO-mice. The neuronal mechanisms of myoclonies in man are largely unknown, and to our knowledge no murine model for non-progressive myoclonic epilepsy is available today. With its varied myoclonic seizures, its well-defined genetic defect, and its specific deviation of synaptic transmission, the DKO-mouse may be a valuable tool in the study of myoclonic epilepsies.