Abstracts

Rationale: The African naked mole-rat (H. glaber) presents a unique opportunity to study the contributions of physiology and environment on neuronal synchrony and seizures. Besides their extreme longevity (> 30 years), and inducible reproductive and stress hormones (as cooperative breeders), naked mole-rats have a wide tolerance for ambient oxygen and carbon dioxide (as fossorial rodents), and a brain temperature that is tightly coupled to the environment (as poikilotherms). In addition, naked mole-rats appear to be prone to seizure, displaying sporadic spontaneous seizure behaviors in vivo and spontaneous hippocampal epileptiform burst discharges in vitro. However, the mechanisms underlying this lowered seizure threshold are not well understood.Methods: To test the possibility that a lowered seizure threshold in the adult naked mole-rat is mediated through a limited brain pH buffering capacity, animals were exposed to hyperthermia (~41°C ambient) or injected with sodium bicarbonate (5 mM/kg i.p.), following the methods of Kaila and colleagues in juvenile rats and mice. Additional animals were injected with the respiratory stimulant nikethamide (100 mg/kg i.p.). Hippocampal slice electrophysiology was used to measure the sensitivity of epileptiform burst discharges to pH.Results: Hyperthermia, bicarbonate and nikethemide produced robust seizure behavior which was confirmed with EEG. Seizures included intermittent generalized convulsions with masticatory automatisms, and showed large amplitude ictal spiking in frontal and hippocampal electrodes. Administration of 5% CO2 in room air suppressed behavioral seizure and ictal activity whereas restoration of normal CO2 was accompanied by renewed seizing. Hippocampal slices confirmed epileptiform activity suppression with hypercapnia and enhncement with hypocapnia.Conclusions: Together, these results suggest that an enhanced sensitivity to brain alkalosis mediates the seizure susceptibility of this species, and posits the naked mole-rat as a new animal model in the study of febrile seizures.