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.
Institute of Neurophysiology, Faculty of Medicine, University of Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany. akp74@uni-koeln.de
Marco
M
Weiergräber
Margit
M
Henry
Matthew S P
MS
Ho
Henrik
H
Struck
Jürgen
J
Hescheler
Toni
T
Schneider
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D020908:Calcium Channels, R-Type / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000502:physiology*; D004569:Electroencephalography; D006885:Hydroxybutyrates / Q000737:chemistry / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010507:Periodicity; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology; D013686:Telemetry; D013788:Thalamus / Q000502:physiology*
C498916:Cacna1e protein, mouse; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D006885:Hydroxybutyrates; D007783:Lactones; C111420:4-hydroxybutyric acid