Respiratory alkalosis provokes spike-wave discharges in seizure-prone rats

被引:1
作者
Salvati, Kathryn A. [1 ,2 ]
Souza, George M. P. R. [1 ]
Lu, Adam C. [1 ,2 ]
Ritger, Matthew L. [1 ,2 ]
Guyenet, Patrice [1 ]
Abbott, Stephen B. [1 ]
Beenhakker, Mark P. [1 ]
机构
[1] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA
[2] Univ Virginia, Neurosci Grad Program, Charlottesville, VA 22901 USA
来源
ELIFE | 2022年 / 11卷
关键词
epilepsy; respiration; thalamus; seizure; pH; Rat; CHILDHOOD ABSENCE EPILEPSY; IDIOPATHIC GENERALIZED EPILEPSY; RETROTRAPEZOID NUCLEUS; THALAMIC NEURONS; CORTICAL FOCUS; PHOX2B-EXPRESSING NEURONS; EPILEPTIFORM DISCHARGES; ALTERED AWARENESS; REFLEX SEIZURES; HYPERVENTILATION;
D O I
10.7554/eLife.72898; 10.7554/eLife.72898.sa0; 10.7554/eLife.72898.sa1; 10.7554/eLife.72898.sa2
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hyperventilation reliably provokes seizures in patients diagnosed with absence epilepsy. Despite this predictable patient response, the mechanisms that enable hyperventilation to powerfully activate absence seizure-generating circuits remain entirely unknown. By utilizing gas exchange manipulations and optogenetics in the WAG/Rij rat, an established rodent model of absence epilepsy, we demonstrate that absence seizures are highly sensitive to arterial carbon dioxide, suggesting that seizure-generating circuits are sensitive to pH. Moreover, hyperventilation consistently activated neurons within the intralaminar nuclei of the thalamus, a structure implicated in seizure generation. We show that intralaminar thalamus also contains pH-sensitive neurons. Collectively, these observations suggest that hyperventilation activates pH-sensitive neurons of the intralaminar nuclei to provoke absence seizures.
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页数:26
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