title: The inhibition of the dorsal paragigantocellular reticular nucleus induces waking and the activation of all adrenergic and noradrenergic neurons: a combined pharmacological and functional neuroanatomical study.
abstract: GABAergic neurons specifically active during paradoxical sleep (PS) localized in the dorsal paragigantocellular reticular nucleus (DPGi) are known to be responsible for the cessation of activity of the noradrenergic neurons of the locus coeruleus during PS. In the present study, we therefore sought to determine the role of the DPGi in PS onset and maintenance and in the inhibition of the LC noradrenergic neurons during this state. The effect of the inactivation of DPGi neurons on the sleep-waking cycle was examined in rats by microinjection of muscimol, a GABAA agonist, or clonidine, an alpha-2 adrenergic receptor agonist. Combining immunostaining of the different populations of wake-inducing neurons with that of c-FOS, we then determined whether muscimol inhibition of the DPGi specifically induces the activation of the noradrenergic neurons of the LC. Slow wave sleep and PS were abolished during 3 and 5 h after muscimol injection in the DPGi, respectively. The application of clonidine in the DPGi specifically induced a significant decrease in PS quantities and delayed PS appearance compared to NaCl. We further surprisingly found out that more than 75% of the noradrenergic and adrenergic neurons of all adrenergic and noradrenergic cell groups are activated after muscimol treatment in contrast to the other wake active systems significantly less activated. These results suggest that, in addition to its already know inhibition of LC noradrenergic neurons during PS, the DPGi might inhibit the activity of noradrenergic and adrenergic neurons from all groups during PS, but also to a minor extent during SWS and waking.
authors.affiliation: INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Team SLEEP, Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Clément
authors.affiliation: INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Team SLEEP, Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Valencia Garcia
authors.affiliation: INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Team SLEEP, Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Paul-Antoine
authors.initials: PA
authors.lastname: Libourel
authors.affiliation: INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Team SLEEP, Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Arthaud
authors.affiliation: INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Team SLEEP, Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Fort
authors.affiliation: INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Team SLEEP, Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Pierre-Hervé
authors.initials: PH
authors.lastname: Luppi
mesh_terms: D059331:Adrenergic Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D008526:Medulla Oblongata / Q000033:anatomy & histology* / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009445:Neuroanatomy; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D009118:Muscimol; D003000:Clonidine