Electrophysiological evidence that noradrenergic neurons of the rat locus coeruleus are tonically inhibited by GABA during sleep.
It is well known that noradrenergic locus coeruleus (LC) neurons decrease their activity during slow wave sleep (SWS) and are virtually quiescent during paradoxical sleep (PS). It has been proposed that a GABAergic input could be directly responsible for this sleep-dependent neuronal inactivation. To test this hypothesis, we used a new method combining polygraphic recordings, microiontophoresis and single-unit extracellular recordings in unanaesthetized head-restrained rats. We found that iontophoretic application of bicuculline, a specific GABA(A)-receptor antagonist, during PS and SWS restore a tonic firing in the LC noradrenergic neurons. We further observed that the application of bicuculline during wakefulness (W) induced an increase of the discharge rate. Of particular importance for the interpretation of these results, using the microdialysis technique, Nitz and Siegel (Neuroscience, 1997; 78: 795) recently found an increase of the GABA release in the cat LC during SWS and PS as compared with waking values. Based on these and our results, we therefore propose that during W, the LC cells are under a GABAergic inhibitory tone which progressively increases at the entrance and during SWS and PS and is responsible for the inactivation of these neurons during these states.
Gervasoni
D
D
Laboratoire de Médecine Expérimentale, INSERM U480, CNRS ERS 5645, Faculté de Pharmacie, Université Claude Bernard Lyon I, France. gervasoni@sommeil.univ-lyon1.fr
Darracq
L
L
Fort
P
P
Soulière
F
F
Chouvet
G
G
Luppi
P H
PH
D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology; D004594:Electrophysiology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007478:Iontophoresis; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D017286:Polysomnography / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012890:Sleep / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid; D009638:Norepinephrine; D001640:Bicuculline