title: Constitutive and Acquired Serotonin Deficiency Alters Memory and Hippocampal Synaptic Plasticity.
abstract: Serotonin (5-HT) deficiency occurs in a number of brain disorders that affect cognitive function. However, a direct causal relationship between 5-HT hypo-transmission and memory and underlying mechanisms has not been established. We used mice with a constitutive depletion of 5-HT brain levels (Pet1KO mice) to analyze the contribution of 5-HT to different forms of learning and memory. Pet1KO mice exhibited a striking deficit in novel object recognition memory, a hippocampal-dependent task. No alterations were found in tasks for social recognition, procedural learning, or fear memory. Viral delivery of designer receptors exclusively activated by designer drugs was used to selectively silence the activity of 5-HT neurons in the raphe. Inhibition of 5-HT neurons in the median raphe, but not the dorsal raphe, was sufficient to impair object recognition in adult mice. In vivo electrophysiology in behaving mice showed that long-term potentiation in the hippocampus of 5-HT-deficient mice was altered, and administration of the 5-HT1A agonist 8-OHDPAT rescued the memory deficits. Our data suggest that hyposerotonergia selectively affects declarative hippocampal-dependent memory. Serotonergic projections from the median raphe are necessary to regulate object memory and hippocampal synaptic plasticity processes, through an inhibitory control mediated by 5-HT1A receptors.
authors.affiliation: Institut du Fer à Moulin, Paris, France.|INSERM, UMRS-839, Paris, France.|University Pierre and Marie Curie, Paris, France.
authors.forename: Sebastian P
authors.initials: SP
authors.lastname: Fernandez
authors.affiliation: Institut du Fer à Moulin, Paris, France.|INSERM, UMRS-839, Paris, France.|University Pierre and Marie Curie, Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Muzerelle
authors.affiliation: Institut du Fer à Moulin, Paris, France.|INSERM, UMRS-839, Paris, France.|University Pierre and Marie Curie, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Scotto-Lomassese
authors.affiliation: Université Côte d'Azur, CNRS, IPMC, Valbonne, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Barik
authors.affiliation: Division of Neurosciences, Pablo de Olavide University, Seville, Spain.
authors.forename: Agnès
authors.initials: A
authors.lastname: Gruart
authors.affiliation: Division of Neurosciences, Pablo de Olavide University, Seville, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Delgado-García
authors.affiliation: Institut du Fer à Moulin, Paris, France.|INSERM, UMRS-839, Paris, France.|University Pierre and Marie Curie, Paris, France.
authors.forename: Patricia
authors.identifier: 0000-0003-4217-5717
authors.initials: P
authors.lastname: Gaspar
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D008297:Male; D008568:Memory / Q000502:physiology*; D000069077:Memory Consolidation / Q000502:physiology; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D011903:Raphe Nuclei / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D021641:Recognition, Psychology / Q000502:physiology; D059326:Serotonergic Neurons / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: C484684:Fev protein, mouse; D014157:Transcription Factors; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin