title: Sleep deprivation-induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus.
abstract: Although the function of sleep remains elusive, there is compelling evidence to suggest that sleep plays an important role in learning and memory. A number of studies have now shown that sleep deprivation (SD) results in significant impairment of long-term potentiation (LTP) in the hippocampus. In this study, we have attempted to determine the mechanisms responsible for this impairment. After 72 h SD using the multiple-platform technique, we observed a reduction in the whole-cell recorded NMDA/AMPA ratio of CA1 pyramidal cells in response to Schaffer collateral stimulation. This impairment was specific to sleep deprivation as rats placed over a single large platform, which allowed sleep, had a normal NMDA/AMPA ratio. mEPSCs evoked by local application of a high osmolarity solution revealed no differences in the AMPA receptor function. NMDA currents recorded from outside-out patches excised from the distal dendrites of CA1 cells displayed a reduction in amplitude after SD. While there were no alterations in the glutamate sensitivity, channel open probability or the single channel conductance of the receptor, a crosslinking assay demonstrated that the NR1 and NR2A subunits of NMDA receptors were preferentially retained in the cytoplasm after SD, indicating that SD alters NMDAR surface expression. In summary, we have identified a potential mechanism underlying SD-induced LTP impairment. This synaptic alteration may underlie the cognitive deficits seen following sleep deprivation and could represent a target for future intervention studies.
authors.affiliation: Neuroscience Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, LA 70115, USA. cmcder@lsuhsc.edu
authors.forename: Carmel M
authors.initials: CM
authors.lastname: McDermott
authors.forename: Mattie N
authors.initials: MN
authors.lastname: Hardy
authors.forename: Nicolas G
authors.initials: NG
authors.lastname: Bazan
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Magee
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012892:Sleep Deprivation / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005998:Glycine