title: Transient inhibition and long-term facilitation of locomotion by phasic optogenetic activation of serotonin neurons.
abstract: Serotonin (5-HT) is associated with mood and motivation but the function of endogenous 5-HT remains controversial. Here, we studied the impact of phasic optogenetic activation of 5-HT neurons in mice over time scales from seconds to weeks. We found that activating dorsal raphe nucleus (DRN) 5-HT neurons induced a strong suppression of spontaneous locomotor behavior in the open field with rapid kinetics (onset ≤1 s). Inhibition of locomotion was independent of measures of anxiety or motor impairment and could be overcome by strong motivational drive. Repetitive place-contingent pairing of activation caused neither place preference nor aversion. However, repeated 15 min daily stimulation caused a persistent increase in spontaneous locomotion to emerge over three weeks. These results show that 5-HT transients have strong and opposing short and long-term effects on motor behavior that appear to arise from effects on the underlying factors that motivate actions.
authors.affiliation: Champalimaud Neuroscience Program, Champalimaud Centre for the Unknown, Lisbon, Portugal.
authors.forename: Patrícia A
authors.initials: PA
authors.lastname: Correia
authors.affiliation: Champalimaud Neuroscience Program, Champalimaud Centre for the Unknown, Lisbon, Portugal.
authors.forename: Eran
authors.initials: E
authors.lastname: Lottem
authors.affiliation: Champalimaud Neuroscience Program, Champalimaud Centre for the Unknown, Lisbon, Portugal.|School of Medicine, University of California, Irvine, United States.
authors.forename: Dhruba
authors.initials: D
authors.lastname: Banerjee
authors.affiliation: Champalimaud Neuroscience Program, Champalimaud Centre for the Unknown, Lisbon, Portugal.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Machado
authors.affiliation: Champalimaud Neuroscience Program, Champalimaud Centre for the Unknown, Lisbon, Portugal.
authors.forename: Megan R
authors.identifier: 0000-0002-4499-1657
authors.initials: MR
authors.lastname: Carey
authors.affiliation: Champalimaud Neuroscience Program, Champalimaud Centre for the Unknown, Lisbon, Portugal.
authors.forename: Zachary F
authors.identifier: 0000-0001-7913-9109
authors.initials: ZF
authors.lastname: Mainen
mesh_terms: D000818:Animals; D001007:Anxiety; D065847:Dorsal Raphe Nucleus / Q000502:physiology*; D008124:Locomotion; D051379:Mice; D009042:Motivation; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists
chemical_list: D017366:Serotonin Receptor Agonists; D012701:Serotonin
keywords: dorsal raphe nucleus; locomotion; mouse; neuroscience; optogenetics; serotonin