title: Nicotinic receptors in mouse prefrontal cortex modulate ultraslow fluctuations related to conscious processing.
abstract: The prefrontal cortex (PFC) plays an important role in cognitive processes, including access to consciousness. The PFC receives significant cholinergic innervation and nicotinic acetylcholine receptors (nAChRs) contribute greatly to the effects of acetylcholine signaling. Using in vivo two-photon imaging of both awake and anesthetized mice, we recorded spontaneous, ongoing neuronal activity in layer II/III in the PFC of WT mice and mice deleted for different nAChR subunits. As in humans, this activity is characterized by synchronous ultraslow fluctuations and neuronal synchronicity is disrupted by light general anesthesia. Both the α7 and β2 nAChR subunits play an important role in the generation of ultraslow fluctuations that occur to a different extent during quiet wakefulness and light general anesthesia. The β2 subunit is specifically required for synchronized activity patterns. Furthermore, chronic application of mecamylamine, an antagonist of nAChRs, disrupts the generation of ultraslow fluctuations. Our findings provide new insight into the ongoing spontaneous activity in the awake and anesthetized state, and the role of cholinergic neurotransmission in the orchestration of cognitive functions.
authors.affiliation: Neurobiologie Intégrative des Systèmes Cholinergiques, Institut Pasteur, Paris F-75724 cedex 15, France; fani.koukouli@pasteur.fr jean-pierre.changeux@pasteur.fr umaskos@pasteur.fr.|CNRS UMR 3571, Institut Pasteur, Paris F-75724 cedex 15, France.
authors.forename: Fani
authors.initials: F
authors.lastname: Koukouli
authors.affiliation: Group for Neural Theory, Laboratoire des Neurosciences Cognitives, INSERM Unité 969, Département d'Études Cognitives, École Normale Supérieure, Paris F-75005, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Rooy
authors.affiliation: CNRS UMR 3571, Institut Pasteur, Paris F-75724 cedex 15, France; fani.koukouli@pasteur.fr jean-pierre.changeux@pasteur.fr umaskos@pasteur.fr.|Chaire de Communications Cellulaires, Collège de France, Paris F-75005, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Changeux
authors.affiliation: Neurobiologie Intégrative des Systèmes Cholinergiques, Institut Pasteur, Paris F-75724 cedex 15, France; fani.koukouli@pasteur.fr jean-pierre.changeux@pasteur.fr umaskos@pasteur.fr.|CNRS UMR 3571, Institut Pasteur, Paris F-75724 cedex 15, France.
authors.forename: Uwe
authors.initials: U
authors.lastname: Maskos
mesh_terms: D000109:Acetylcholine / Q000737:chemistry; D000768:Anesthesia, General; D000818:Animals; D003243:Consciousness / Q000502:physiology*; D017353:Gene Deletion; D007530:Isoflurane / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D007530:Isoflurane; D000109:Acetylcholine
keywords: anesthesia; consciousness; nicotinic receptor; prefrontal cortex; ultraslow fluctuations