[Abstract Title]. - Society for Neuroscience

Poster
285. Sleep: Molecular, Cellular and Pharmacology I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 285.9/QQ25
Topic: E.08.c. Sleep: Molecular, cellular, and pharmacology
Support: NSF Pickwick Postdoctoral Research Fellowship
Title: Role of gene transcription and translation during sleep-dependent cortical plasticity
Authors: *J. SEIBT, S. J. ATON, T. COLEMAN, M. C. DUMOULIN, M. G. FRANK;
Neurosci., Univ. Pennsylvania, Philadelphia, PA
Abstract:
Sleep is hypothesized to consolidate memory, but the cellular mechanisms governing this process are unknown. One critical step
in the consolidation of both memory and synaptic plasticity is gene transcription and translation. We examined the role of both processes in a
classic form of in vivo plasticity that is triggered by monocular deprivation (MD) and consolidated by sleep (ocular dominance plasticitym, ODP).
We used western blots and quantitative RT-PCR to assess changes in mRNA and protein expression of plasticity related genes in primary visual
cortex in animals undergoing different manipulations of binocular vision and sleep. Immunochemistry was also used to determine activation of
mTOR and eEF2 protein synthesis regulatory pathways. In separate experiments, we determined the necessity of protein synthesis for sleep-
dependent ODP by locally inhibiting (during sleep) the mTOR pathway with rapamycin and global cortical protein synthesis with cycloheximide.
Following intracortical infusion, ODP was assessed with intrinsic signal imaging and micro-electrode recording
Preliminary western-blot analyses suggest a simultaneous activation of the mTOR and the eEF2 pathways in the remodeling V1 during sleep
consistent with a coordinate process of enhanced translation initiation and reduced peptide chain elongation. RT-PCR performed on the same
tissues showed a decrease of 50 to 80% of immediate-early genes (Arc, c-Fos) during sleep specifically after MD compared to control sleeping
animals (no MD). Surprisingly, this decrease in Arc mRNA expression is accompanied by an increased expression of the corresponding protein in
post-MD sleep. The requirement of de novo protein synthesis during sleep-dependent ODP was further confirmed by our results showing that
both cycloheximide and rapamycin infusions during sleep impair the consolidation of ODP.
Taken together, our results indicate that sleep promotes mechanisms implicated in „local‟ dendritic protein synthesis (activation of mTOR
pathway, increase in Arc protein expression) and that this process is accompanied by a shut-down of general translation (eEF2 phosphorylation)
and transcription (decrease mRNA expression of IEGs).
Disclosures: J. Seibt , None; S.J. Aton, None; T. Coleman, None; M.C. Dumoulin,
None; M.G. Frank, None.