title: Sleep fragmentation reduces hippocampal CA1 pyramidal cell excitability and response to adenosine.
abstract: Sleep fragmentation (SF) impairs the restorative/cognitive benefits of sleep via as yet unidentified alterations in neural physiology. Previously, we found that hippocampal synaptic plasticity and spatial learning are impaired in a rat model of SF which utilizes a treadmill to awaken the animals every 2 min, mimicking the frequency of awakenings observed in human sleep apnea patients. Here, we investigated the cellular mechanisms responsible for these effects, using whole-cell patch-clamp recordings. 24h of SF decreased the excitability of hippocampal CA1 pyramidal neurons via decreased input resistance, without alterations in other intrinsic membrane or action potential properties (when compared to cage controls, or to exercise controls that experienced the same total amount of treadmill movement as SF rats). Contrary to our initial prediction, the hyperpolarizing response to bath applied adenosine (30 microM) was reduced in the CA1 neurons of SF treated rats. Our initial prediction was based on the evidence that sleep loss upregulates cortical adenosine A1 receptors; however, the present findings are consistent with a very recent report that hippocampal A1 receptors are not elevated by sleep loss. Thus, increased adenosinergic inhibition is unlikely to be responsible for reduced hippocampal long-term potentiation in SF rats. Instead, the reduced excitability of CA1 pyramidal neurons observed here may contribute to the loss of hippocampal long-term potentiation and hippocampus-dependent cognitive impairments associated with sleep disruption.
authors.affiliation: VA Boston Healthcare System and Harvard Medical School, Research 151-C, 940 Belmont Street, Brockton, MA 02301, USA.
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Tartar
authors.forename: James T
authors.initials: JT
authors.lastname: McKenna
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Ward
authors.forename: Robert W
authors.initials: RW
authors.lastname: McCarley
authors.forename: Robert E
authors.initials: RE
authors.lastname: Strecker
authors.forename: Ritchie E
authors.initials: RE
authors.lastname: Brown
mesh_terms: D000200:Action Potentials; D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000096:biosynthesis; D012892:Sleep Deprivation; D013570:Synaptic Membranes / Q000502:physiology; D015854:Up-Regulation
chemical_list: D043682:Receptor, Adenosine A1; D000241:Adenosine