title: Activation of raphe nuclei triggers rapid and distinct effects on parallel olfactory bulb output channels.
abstract: The serotonergic raphe nuclei are involved in regulating brain states over timescales of minutes and hours. We examined more rapid effects of raphe activation on two classes of principal neurons in the mouse olfactory bulb, mitral and tufted cells, which send olfactory information to distinct targets. Brief stimulation of the raphe nuclei led to excitation of tufted cells at rest and potentiation of their odor responses. While mitral cells at rest were also excited by raphe activation, their odor responses were bidirectionally modulated, leading to improved pattern separation of odors. In vitro whole-cell recordings revealed that specific optogenetic activation of raphe axons affected bulbar neurons through dual release of serotonin and glutamate. Therefore, the raphe nuclei, in addition to their role in neuromodulation of brain states, are also involved in fast, sub-second top-down modulation similar to cortical feedback. This modulation can selectively and differentially sensitize or decorrelate distinct output channels.
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.|Department of Molecular &Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Vikrant
authors.initials: V
authors.lastname: Kapoor
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.|Department of Molecular &Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Allison C
authors.initials: AC
authors.lastname: Provost
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.|Department of Molecular &Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Prateek
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.|Department of Molecular &Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Venkatesh N
authors.identifier: http://orcid.org/0000-0003-2443-4252
authors.initials: VN
authors.lastname: Murthy
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000502:physiology; D000075402:Channelrhodopsins; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology*; D009833:Olfactory Pathways / Q000502:physiology*; D062308:Optogenetics; D011903:Raphe Nuclei / Q000166:cytology / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D012903:Smell / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000235:genetics
chemical_list: D000075402:Channelrhodopsins; D012701:Serotonin; D018698:Glutamic Acid; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase