Rationale
Previous work from our laboratory demonstrated that vagus nerve activity (VNA) during absence seizures in GAERS (Genetic Absence Epilepsy Rats from Strasbourg) varies with cumulative seizure burden, suggesting progressive parasympathetic dysfunction. Respiratory disturbances, including apnea, are a major contributor to epilepsy-related morbidity and to the risk of sudden unexpected death in epilepsy (SUDEP), and hypercapnia provides a physiologically relevant stressor for probing autonomic control. Impaired vagal recruitment or maladaptive sympathetic compensation during respiratory challenge may critically destabilise cardiorespiratory homeostasis. We therefore sought to quantify VNA responses to hypercapnic challenge as a functional index of autonomic integrity, while simultaneously examining modulation by vigilance state.
Methods
Freely moving healthy rats (n = 9), 4.5-month-old GAERS (n = 7), and 11.5-month-old GAERS (n = 7) were implanted under sevoflurane anesthesia with epidural EEG electrodes and intraneural vagus nerve electrodes, along with extraneural control electrodes. Following 24 h of continuous baseline recording, animals underwent a 3-h experimental protocol consisting of normocapnic baseline, 10% CO₂ exposure, and recovery. VNA was quantified using compound action potential (CAP) detection based on local-maxima thresholding, with neural-specific events identified by excluding signals coincident with control electrodes.
Results
Hypercapnia significantly increased VNA in GAERS rats, whereas in non-epileptic controls (NEC) VNA remained stable during CO₂ exposure and exhibited a pronounced rebound during recovery. This post-hypercapnic rebound was absent in epileptic animals, indicating disrupted autonomic responsiveness to respiratory stress.
Conclusion
Altered vagal responses to hypercapnic challenge reveal autonomic dysregulation in epilepsy, supporting vagus nerve activity as a sensitive biomarker of impaired respiratory–autonomic coupling and SUDEP-related vulnerability.
Collard, E., Germany Morrison, E. I., El Tahry, R., Nonclercq, A., & et al. (2026, July 9). Deciphering Autonomic Dysregulation in Epilepsy Through Vagus Nerve Activity. FENS 2026, Barcelona. https://hdl.handle.net/2078.5/279039