title: Serotonin differentially modulates excitatory and inhibitory synaptic inputs to putative sleep-promoting neurons of the ventrolateral preoptic nucleus.
abstract: The role of serotonin (5-HT) in sleep-wake regulation has been a subject of intense debate and remains incompletely understood. In the ventrolateral preoptic nucleus (VLPO), the main structure that triggers non-rapid eye movement (NREM) sleep, putative sleep-promoting (PSP) neurons were shown ex vivo to be either inhibited (Type-1) or excited (Type-2) by 5-HT application. To determine the complex action of this neurotransmitter on PSP neurons, we recorded spontaneous and miniature excitatory and inhibitory postsynaptic currents (sEPSCs, sIPSCs, mEPSCs and mIPSCs) in response to bath application of 5-HT. We established in mouse acute VLPO slices that 5-HT reduces spontaneous and miniature EPSC and IPSC frequencies to Type-1 neurons, whereas 5-HT selectively increases sIPSC and mIPSC frequencies to Type-2 VLPO neurons. We further determined that Type-1 neurons display a lower action potential threshold and a smaller soma size than Type-2 neurons. Finally, single-cell RT-PCR designed to identify the 13 serotonergic receptor subtypes revealed the specific mRNA expression of the 5-HT1A,B,D,F receptors by Type-1 neurons. Furthermore, the 5-HT2A-C,4,7 receptors were found to be equivalently expressed by both neuronal types. Altogether, our results establish that the excitatory and inhibitory inputs to Type-1 and Type-2 VLPO PSP neurons are differentially regulated by 5-HT. Electrophysiological, morphological and molecular differences were also identified between these two neuronal types. Our results provide new insights regarding the orchestration of sleep regulation by 5-HT release, and strongly suggest that Type-2 neurons could play a permissive role, whereas Type-1 neurons could have an executive role in sleep induction and maintenance.
authors.affiliation: Brain Plasticity Unit, ESPCI ParisTech, Paris, France; Centre National de la Recherche Scientifique, UMR 8249, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Sangare
authors.affiliation: Brain Plasticity Unit, ESPCI ParisTech, Paris, France; Centre National de la Recherche Scientifique, UMR 8249, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Dubourget
authors.affiliation: Brain Plasticity Unit, ESPCI ParisTech, Paris, France; Centre National de la Recherche Scientifique, UMR 8249, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Geoffroy
authors.affiliation: Brain Plasticity Unit, ESPCI ParisTech, Paris, France; Centre National de la Recherche Scientifique, UMR 8249, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gallopin
authors.affiliation: Brain Plasticity Unit, ESPCI ParisTech, Paris, France; Centre National de la Recherche Scientifique, UMR 8249, France. Electronic address: armelle.rancillac@college-de-france.fr.
authors.forename: Armelle
authors.initials: A
authors.lastname: Rancillac
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology* / Q000502:physiology; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin
keywords: 8-OH-DPAT (PubChem CID: 6917794); EPSCs; Gal-GFP neurons; IPSCs; NREM; PF03246799 hydrochloride (PubChem CID 67097843); Single-cell RT-PCR; VLPO; bicuculline (PubChem CID: 104871); kynurinic acid (PubChem CID: 3845); noradrenaline (PubChem CID: 297812); serotonin (PubChem CID: 160436); tetrodotoxin (PubChem CID: 16759596)