@misc{oai:ir.soken.ac.jp:00001150, author = {佐々木, 幸恵 and ササキ, サチエ and SASAKI, Sachie}, month = {2016-02-17, 2016-02-17}, note = {Homozygous tottering (tg) mice have a mutation in the voltage-dependent Cav2.1　(P/Q-type) calcium channel α₁ 2.1 subunit gene. tg mice show not only cerebellar　ataxia but also absence epilepsy, which begins at about 3 weeks of age and persist　throughout life. Similarities in EEG abnormality and in pharmacological sensitivity　to antiepileptic drugs suggest that tg mice can serve as a model of human absence　epilepsy. To identify the mechanism of epileptogenesis, I studied the effect of　the calcium channel mutation on the thalamocortical network using whole-cell patch　clamp recordings in brain slice preparations.
The amplitude of inhibitory postsynaptic currents (IPSC) recorded from layer　IV pyramidal cells of the cerebral cortex in response to thalamic stimulation became　disproportionately reduced, compared with the amplitude of excitatory postsynaptic　currents (EPSC), in the later developmental stage (P21-30). Similar results that　the IPSC amplitude, but not the EPSC amplitude was drastically diminished were　obtained by local stimulation in layer IV pyramidal neurons. However the reduction of the IPSC amplitude was not seen in layer V pyramidal neurons or in layer IV　pyramidal neurons of younger tg mice before the onset of epilepsy (P14-16).
Furthermore, recordings of multiple field potentials revealed that cortical　excitation evoked by layer IV stimulation spread more widely in epileptic tg than　in control or non-epileptic tg mice, although the area of excitation was confined　within a barrel. These results demonstrated a close relationship between impaired　IPSCs in layer IV and absence epilepsy, and suggested that the defect of the　feed-forward inhibition in the cortical input layer is associated with the　generation of absence epilepsy in tg mice., application/pdf, 総研大甲第815号}, title = {Cellular mechanism of absence epilepsy in calcium channel mutant mice}, year = {} }