Wakefulness Affects Synaptic and Network Activity by Increasing Extracellular, Astrocyte Derived Adenosine: Astrocytes Control Wakefulness-Driven Adenosine
| Autor: | Schmitt, L. Ian, Sims, Robert E., Dale, Nicholas, Haydon, Philip G. |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Cerebral Cortex
Male Adenosine Receptor Adenosine A1 Vesicle-Associated Membrane Protein 2 Excitatory Postsynaptic Potentials Extracellular Fluid Mice Transgenic In Vitro Techniques Hippocampus Synaptic Transmission Article Mice Inbred C57BL Mice Theophylline Astrocytes Animals Sleep Deprivation Female Wakefulness |
| Popis: | Loss of sleep causes an increase in sleep drive and deficits in hippocampal-dependent memory. Both of these responses are thought to require activation of adenosine A1 receptors (adorA1Rs) and release of transmitter molecules including ATP, which is rapidly converted to adenosine in the extracellular space, from astrocytes in a process termed gliotransmission. Although it is increasingly clear that astrocyte-derived adenosine plays an important role in driving the homeostatic sleep response and the effects of sleep loss on memory (Halassa et al., 2009; Florian et al., 2011), previous studies have not determined whether the concentration of this signaling molecule increases in response to wakefulness. Here, we show that the level of adorA1R activation increases in response to wakefulness in mice (Mus musculus). We found that this increase affected synaptic transmission in the hippocampus and modulated network activity in the cortex. Direct biosensor-based measurement of adenosine showed that the net extracellular concentration of this transmitter increased in response to normal wakefulness and sleep deprivation. Genetic inhibition of gliotransmission prevented this increase and attenuated the wakefulness-dependent changes in synaptic and network regulation by adorA1R. Consequently, we conclude that wakefulness increases the level of extracellular adenosine in the hippocampus and that this increase requires the release of transmitters from astroctyes. |
| Databáze: | OpenAIRE |
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