Experience-dependent upregulation of multiple plasticity factors in the hippocampus during early REM sleep

Author(s)

Calais, Julien Braga ^{[1, 2]} ; Ojopi, Elida Benquique ^[2] ; Morya, Edgard ^{[3, 1]} ; Sameshima, Koichi ^{[4, 1]} ; Ribeiro, Sidarta ^[5]

Affiliation

^[1] Hosp Sirio Libanes, Inst Ensino & Pesquisa, Lab Cesar Timo Iaria, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Lab Neurociencias LIM 27, Hosp Clin, Fac Med, Dept & Inst Psiquiatria, Sao Paulo - Brazil

^[3] Edmond & Lily Safra Int Inst Neurosci Natal ELS I, Natal, RN - Brazil

^[4] Univ Sao Paulo, Fac Med, Dept Radiol & Oncol, Sao Paulo - Brazil

^[5] Univ Fed Rio Grande Norte UFRN, Inst Cerebro, BR-5905645 Natal, RN - Brazil

• Document type: Journal article
• Source: NEUROBIOLOGY OF LEARNING AND MEMORY; v. 122, p. 19-27, JUL 2015.
• Web of Science Citations: 14

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. (C) 2015 The Authors. Published by Elsevier Inc. (AU)

• FAPESP's process: 06/05436-8 - Gene expression during sleep after exposure to an enriched environment
• Grantee: Julien Braga Calais Correia Pinto
• Support Opportunities: Scholarships in Brazil - Master