A role for the preoptic sleep-promoting system in absence epilepsy.
Absence epilepsy (AE) in humans and the genetic AE model in WAG/Rij rats are both associated with abnormalities in sleep architecture that suggest insufficiency of the sleep-promoting mechanisms. In this study we compared the functionality of sleep-active neuronal groups within two well-established sleep-promoting sites, the ventrolateral and median preoptic nuclei (VLPO and MnPN, respectively), in WAG/Rij and control rats. Neuronal activity was assessed using c-Fos immunoreactivity and chronic single-unit recording techniques. We found that WAG/Rij rats exhibited a lack of sleep-associated c-Fos activation of GABAergic MnPN and VLPO neurons, a lower percentage of MnPN and VLPO cells increasing discharge during sleep and reduced firing rates of MnPN sleep-active neurons, compared to non-epileptic rats. The role of sleep-promoting mechanisms in pathogenesis of absence seizures was assessed in non-epileptic rats using electrical stimulation and chemical manipulations restricted to the MnPN. We found that fractional activation of the sleep-promoting system in waking was sufficient to elicit absence-like seizures. Given that reciprocally interrelated sleep-promoting and arousal neuronal groups control thalamocortical excitability, we hypothesize that malfunctioning of sleep-promoting system results in impaired ascending control over thalamocortical rhythmogenic mechanisms during wake-sleep transitions thus favoring aberrant thalamocortical oscillations. Our findings suggest a pathological basis for AE-associated sleep abnormalities and a mechanism underlying association of absence seizures with wake-sleep transitions.
Suntsova
N
N
Research Service, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, CA 91343, USA. suntsova@ucla.edu
Kumar
S
S
Guzman-Marin
R
R
Alam
M N
MN
Szymusiak
R
R
McGinty
D
D
D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography; D004832:Epilepsy, Absence / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D011301:Preoptic Area / Q000473:pathology / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology; D014851:Wakefulness / Q000235:genetics
D016760:Proto-Oncogene Proteins c-fos; D005968:Glutamate Decarboxylase