Rapid eye movement sleep and hippocampal theta oscillations precede seizure onset in the tetanus toxin model of temporal lobe epilepsy.
Improved understanding of the interaction between state of vigilance (SOV) and seizure onset has therapeutic potential. Six rats received injections of tetanus toxin (TeTX) in the ventral hippocampus that resulted in chronic spontaneous seizures. The distribution of SOV before 486 seizures was analyzed for a total of 19 d of recording. Rapid eye movement sleep (REM) and exploratory wake, both of which express prominent hippocampal theta rhythm, preceded 47 and 34%, for a total of 81%, of all seizures. Nonrapid eye movement sleep (NREM) and nonexploratory wake, neither of which expresses prominent theta, preceded 6.8 and 13% of seizures. We demonstrate that identification of SOV yields significant differentiation of seizure susceptibilities, with the instantaneous seizure rate during REM nearly 10 times higher than baseline and the rate for NREM less than half of baseline. Survival analysis indicated a shorter duration of preseizure REM bouts, with a maximum transition to seizure at ∼90 s after the onset of REM. This study provides the first analysis of a correlation between SOV and seizure onset in the TeTX model of temporal lobe epilepsy, as well as the first demonstration that hippocampal theta rhythms associated with natural behavioral states can serve a seizure-promoting role. Our findings are in contrast with previous studies suggesting that the correlations between SOV and seizures are primarily governed by circadian oscillations and the notion that hippocampal theta rhythms inhibit seizures. The documentation of significant SOV-dependent seizure susceptibilities indicates the potential utility of SOV and its time course in seizure prediction and control.
Center for Neural Engineering, Departments of Engineering Science and Mechanics, Neurosurgery, Physics, and Bioengineering, Pennsylvania State University, University Park, Pennsylvania 16802, and Children's National Medical Center, George Washington University, Washington, DC 20010.
Madineh
M
Sedigh-Sarvestani
Godfrey I
GI
Thuku
Sridhar
S
Sunderam
Anjum
A
Parkar
Steven L
SL
Weinstein
Steven J
SJ
Schiff
Bruce J
BJ
Gluckman
D000818:Animals; D001143:Arousal / Q000502:physiology*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D009498:Neurotoxins / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans; D012895:Sleep, REM / Q000502:physiology*; D013744:Tetanus Toxin / Q000633:toxicity; D013826:Theta Rhythm / Q000502:physiology*
D009498:Neurotoxins; D013744:Tetanus Toxin
epilepsy; hippocampal theta; preseizure state; rapid eye movement; sleep; tetanus toxin