Key Electrophysiological, Molecular, and Metabolic Signatures of Sleep and Wakefulness Revealed in Primary Cortical Cultures

Autor: Paul Franken, Johan Auwerx, Thomas Curie, Riekelt H. Houtkooper, Mehdi Tafti, Cyril Mikhail, Sylvain Pradervand, Valérie Hinard
Přispěvatelé: Laboratory Genetic Metabolic Diseases
Rok vydání: 2012
Předmět:
Zdroj: Journal of Neuroscience, vol. 32, no. 36, pp. 12506-12517
Journal of neuroscience, 32(36), 12506-12517. Society for Neuroscience
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.2306-12.2012
Popis: Although sleep is defined as a behavioral state, at the cortical level sleep has local and use-dependent features suggesting that it is a property of neuronal assemblies requiring sleep in function of the activation experienced during prior wakefulness. Here we show that mature cortical cultured neurons display a default state characterized by synchronized burst–pause firing activity reminiscent of sleep. This default sleep-like state can be changed to transient tonic firing reminiscent of wakefulness when cultures are stimulated with a mixture of waking neurotransmitters and spontaneously returns to sleep-like state. In addition to electrophysiological similarities, the transcriptome of stimulated cultures strikingly resembles the cortical transcriptome of sleep-deprived mice, and plastic changes as reflected by AMPA receptors phosphorylation are also similar. We used ourin vitromodel and sleep-deprived animals to map the metabolic pathways activated by waking. Only a few metabolic pathways were identified, including glycolysis, aminoacid, and lipids. Unexpectedly large increases in lysolipids were found bothin vivoafter sleep deprivation andin vitroafter stimulation, strongly suggesting that sleep might play a major role in reestablishing the neuronal membrane homeostasis. With ourin vitromodel, the cellular and molecular consequences of sleep and wakefulness can now be investigated in a dish.
Databáze: OpenAIRE