title: Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss.
abstract: The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, havekesr@sas.upenn.edu abele@sas.upenn.edu.
authors.forename: Robbert
authors.initials: R
authors.lastname: Havekes
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, Center for Behavior and Neurosciences, University of Groningen, Groningen, The Netherlands, and.
authors.forename: Vibeke M
authors.initials: VM
authors.lastname: Bruinenberg
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Tudor
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Ferri
authors.affiliation: Forschungszentrum Jülich, Institute of Complex Systems, Zelluläre Biophysik (ICS-4), D-52425 Jülich, Germany.
authors.forename: Arnd
authors.initials: A
authors.lastname: Baumann
authors.affiliation: Center for Behavior and Neurosciences, University of Groningen, Groningen, The Netherlands, and.
authors.forename: Peter
authors.initials: P
authors.lastname: Meerlo
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, havekesr@sas.upenn.edu abele@sas.upenn.edu.
authors.forename: Ted
authors.initials: T
authors.lastname: Abel
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000235:genetics / Q000523:psychology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism* / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects; D017982:Receptors, Biogenic Amine / Q000187:drug effects / Q000235:genetics; D012892:Sleep Deprivation / Q000235:genetics / Q000378:metabolism* / Q000523:psychology*
chemical_list: D017982:Receptors, Biogenic Amine; C027604:norsynephrine receptor; D004247:DNA; D000242:Cyclic AMP
keywords: hippocampus; learning; memory; pharmacogenetics; sleep; sleep disruption