title: Glutamatergic stimulation of the basal forebrain elevates extracellular adenosine and increases the subsequent sleep.
abstract: A prolonged period of waking accumulates sleep pressure, increasing both the duration and the intensity of the subsequent sleep period. Delta power, which is calculated from the slow range electroencephalographic (EEG) oscillations (0.1-4 Hz), is regarded as the marker of sleep intensity. Recent findings indicate that not only the duration but also the quality of waking, determines the level of increase in the delta activity during the subsequent sleep period. Elevated levels of extracellular adenosine in the basal forebrain (BF) during prolonged waking have been proposed to act as the molecular signal of increased sleep pressure, but the role of BF neuronal activity in elevating adenosine has not been previously explored. We hypothesized that an increase in neuronal discharge in the BF would lead to increase in the extracellular adenosine and contribute to the increase in the subsequent sleep. To experimentally increase neuronal activity in the rat BF, we used 3 h in vivo microdialysis application of glutamate or its receptor agonists N-methyl-D-aspartate (NMDA) or AMPA. Samples for adenosine measurement were collected during the drug application and the EEG was recorded during and after the treatment, altogether for 24 h. All treatments increased the duration of the subsequent sleep following the application. In contrast, delta power was elevated only if both the waking EEG theta (5-9 Hz) power (which can be regarded as a marker of active waking) and the extracellular adenosine in the BF were increased during the application. These results indicate that increased neuronal activity in the BF, and particularly the type of neuronal activity coinciding with active waking, is one of the factors contributing to the buildup of the sleep pressure.
authors.affiliation: Institute of Biomedicine Physiology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: H-K
authors.initials: HK
authors.lastname: Wigren
authors.forename: M
authors.initials: M
authors.lastname: Schepens
authors.forename: V
authors.initials: V
authors.lastname: Matto
authors.forename: D
authors.initials: D
authors.lastname: Stenberg
authors.forename: T
authors.initials: T
authors.lastname: Porkka-Heiskanen
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004569:Electroencephalography / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis / Q000379:methods; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D017286:Polysomnography; D016548:Prosencephalon / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016761:Oncogene Proteins v-fos; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D000241:Adenosine