title: Cholinergic neurons of the basal forebrain mediate biochemical and electrophysiological mechanisms underlying sleep homeostasis.
abstract: The tight coordination of biochemical and electrophysiological mechanisms underlies the homeostatic sleep pressure (HSP) produced by sleep deprivation (SD). We have reported that during SD the levels of inducible nitric oxide synthase (iNOS), extracellular nitric oxide (NO), adenosine [AD]ex , lactate [Lac]ex and pyruvate [Pyr]ex increase in the basal forebrain (BF). However, it is not clear whether all of them contribute to HSP leading to increased electroencephalogram (EEG) delta activity during non-rapid eye movement (NREM) recovery sleep (RS) following SD. Previously, we showed that NREM delta increase evident during RS depends on the presence of BF cholinergic (ChBF) neurons. Here, we investigated the role of ChBF cells in coordination of biochemical and EEG changes seen during SD and RS in the rat. Increases in low-theta power (5-7 Hz), but not high-theta (7-9 Hz), during SD correlated with the increase in NREM delta power during RS, and with the changes in nitrate/nitrite [NOx ]ex and [AD]ex . Lesions of ChBF cells using IgG 192-saporin prevented increases in [NOx ]ex , [AD]ex and low-theta activity, during SD, but did not prevent increases in [Lac]ex and [Pyr]ex . Infusion of NO donor DETA NONOate into the saporin-treated BF failed to increase NREM RS and delta power, suggesting ChBF cells are important for mediating NO homeostatic effects. Finally, SD-induced iNOS was mostly expressed in ChBF cells, and the intensity of iNOS induction correlated with the increase in low-theta activity. Together, our data indicate ChBF cells are important in regulating the biochemical and EEG mechanisms that contribute to HSP.
authors.affiliation: VA Boston Healthcare System and Harvard Medical School, 1400 V.F.W. Parkway, West Roxbury, MA, 02067, USA.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Kalinchuk
authors.forename: Tarja
authors.initials: T
authors.lastname: Porkka-Heiskanen
authors.forename: Robert W
authors.initials: RW
authors.lastname: McCarley
authors.forename: Radhika
authors.initials: R
authors.lastname: Basheer
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D066187:Basal Forebrain / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D059329:Cholinergic Neurons / Q000187:drug effects / Q000502:physiology*; D003700:Delta Rhythm / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology; D019289:Pyruvic Acid / Q000378:metabolism; D017208:Rats, Wistar; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology; D013826:Theta Rhythm / Q000187:drug effects / Q000502:physiology
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D009603:Nitroso Compounds; D054789:Ribosome Inactivating Proteins, Type 1; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D019344:Lactic Acid; D019289:Pyruvic Acid; D000076985:Saporins; D000241:Adenosine
keywords: adenosine; inducible nitric oxide synthase; nitric oxide; rat