title: Experience-dependent upregulation of multiple plasticity factors in the hippocampus during early REM sleep.
abstract: Sleep is beneficial to learning, but the underlying mechanisms remain controversial. The synaptic homeostasis hypothesis (SHY) proposes that the cognitive function of sleep is related to a generalized rescaling of synaptic weights to intermediate levels, due to a passive downregulation of plasticity mechanisms. A competing hypothesis proposes that the active upscaling and downscaling of synaptic weights during sleep embosses memories in circuits respectively activated or deactivated during prior waking experience, leading to memory changes beyond rescaling. Both theories have empirical support but the experimental designs underlying the conflicting studies are not congruent, therefore a consensus is yet to be reached. To advance this issue, we used real-time PCR and electrophysiological recordings to assess gene expression related to synaptic plasticity in the hippocampus and primary somatosensory cortex of rats exposed to novel objects, then kept awake (WK) for 60 min and finally killed after a 30 min period rich in WK, slow-wave sleep (SWS) or rapid-eye-movement sleep (REM). Animals similarly treated but not exposed to novel objects were used as controls. We found that the mRNA levels of Arc, Egr1, Fos, Ppp2ca and Ppp2r2d were significantly increased in the hippocampus of exposed animals allowed to enter REM, in comparison with control animals. Experience-dependent changes during sleep were not significant in the hippocampus for Bdnf, Camk4, Creb1, and Nr4a1, and no differences were detected between exposed and control SWS groups for any of the genes tested. No significant changes in gene expression were detected in the primary somatosensory cortex during sleep, in contrast with previous studies using longer post-stimulation intervals (>180 min). The experience-dependent induction of multiple plasticity-related genes in the hippocampus during early REM adds experimental support to the synaptic embossing theory.
authors.affiliation: Laboratório de Neurociências (LIM/27), Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (USP), Departamento e Instituto de Psiquiatria, São Paulo, Brazil; Laboratório Cesar Timo-Iaria, Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, São Paulo, Brazil.
authors.forename: Julien Braga
authors.initials: JB
authors.lastname: Calais
authors.affiliation: Laboratório de Neurociências (LIM/27), Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (USP), Departamento e Instituto de Psiquiatria, São Paulo, Brazil.
authors.forename: Elida Benquique
authors.initials: EB
authors.lastname: Ojopi
authors.affiliation: Laboratório Cesar Timo-Iaria, Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, São Paulo, Brazil; Edmond and Lily Safra International Institute of Neuroscience of Natal (ELS-IINN), Natal, Brazil.
authors.forename: Edgard
authors.initials: E
authors.lastname: Morya
authors.affiliation: Laboratório Cesar Timo-Iaria, Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, São Paulo, Brazil; Departamento de Radiologia e Oncologia, Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, Brazil. Electronic address: ksameshi@usp.br.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sameshima
authors.affiliation: Instituto do Cérebro, Universidade Federal do Rio Grande do Norte (UFRN), Natal, Brazil. Electronic address: sidartaribeiro@neuro.ufrn.br.
authors.forename: Sidarta
authors.initials: S
authors.lastname: Ribeiro
mesh_terms: D000818:Animals; D005106:Exploratory Behavior / Q000502:physiology; D015870:Gene Expression; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012895:Sleep, REM / Q000235:genetics / Q000502:physiology*; D013003:Somatosensory Cortex / Q000502:physiology
keywords: Gene expression; Immediate early genes; Memory; Protein phosphatase 2A; Sleep; Synaptic plasticity