Electrical coupling: novel mechanism for sleep-wake control.
OBJECTIVE
Recent evidence suggests that certain anesthetic agents decrease electrical coupling, whereas the stimulant modafinil appears to increase electrical coupling. We investigated the potential role of electrical coupling in 2 reticular activating system sites, the subcoeruleus nucleus and in the pedunculopontine nucleus, which has been implicated in the modulation of arousal via ascending cholinergic activation of intralaminar thalamus and descending activation of the subcoeruleus nucleus to generate some of the signs of rapid eye movement sleep.


METHODS
We used 6- to 30-day-old rat pups to obtain brainstem slices to perform whole-cell patch-clamp recordings.


RESULTS
Recordings from single cells revealed the presence of spikelets, manifestations of action potentials in coupled cells, and of dye coupling of neurons in the pedunculopontine nucleus. Recordings in pairs of pedunculopontine nucleus and subcoeruleus nucleus neurons revealed that some of these were electrically coupled with coupling coefficients of approximately 2%. After blockade of fast synaptic transmission, the cholinergic agonist carbachol was found to induce rhythmic activity in pedunculopontine nucleus and subcoeruleus nucleus neurons, an effect eliminated by the gap junction blockers carbenoxolone or mefloquine. The stimulant modafinil was found to decrease resistance in neurons in the pedunculopontine nucleus and subcoeruleus nucleus after fast synaptic blockade, indicating that the effect may be due to increased coupling.


CONCLUSIONS
The finding of electrical coupling in specific reticular activating system cell groups supports the concept that this underlying process behind specific neurotransmitter interactions modulates ensemble activity across cell populations to promote changes in sleep-wake state.
Center for Translational Neuroscience, Department of Neurobiology & Dev. Sci., University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. GarciaRillEdgar@uams.edu
Edgar
E
Garcia-Rill
David S
DS
Heister
Meijun
M
Ye
Amanda
A
Charlesworth
Abdallah
A
Hayar
D000818:Animals; D001143:Arousal; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D023902:Chromosome Pairing / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D008297:Male; D000077408:Modafinil; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012154:Reticular Formation / Q000502:physiology; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D018679:Cholinergic Agonists; D002217:Carbachol; D000077408:Modafinil