Altered thalamocortical rhythmicity in Ca(v)2.3-deficient mice

Voltage-gated calcium channels (VGCCs) are key regulators of neuronal excitability and important factors in epileptogenesis and neurodegeneration. Recent findings suggest a novel, important proictogenic and proneuroapoptotic role of the Ca(v)2.3 E/R-type VGCCs in convulsive generalized tonic-clonic and hippocampal seizures. Though Ca(v)2.3 is also expressed in key structures of the thalamocortical circuitry, their functional relevance in non-convulsive absence seizure activity remains unknown. To this end, we investigated absence specific spike-wave discharge (SWD) susceptibility in control and Ca(v)2.3-deficient mice by systemic administration of gamma-hydroxybutyrolactone (GBL, 70 mg/kg i.p.), followed by electrocorticographic radiotelemetric recordings, behavioral analysis and histomorphological characterization. Based on motoric studies, SWD and power-spectrum density (PSD) analysis, our results demonstrate that Ca(v)2.3(-/-) mice exhibit increased absence seizure susceptibility and altered absence seizure architecture compared to control animals. This study provides evidence for the first time that Ca(v)2.3 E/R-type Ca2+ channels are important in modulating thalamocortical hyperoscillation exerting anti-epileptogenic effects in non-convulsive absence seizures.