An adenosine-mediated glial-neuronal circuit for homeostatic sleep

Theresa Bjorness, Nicholas Dale, Gabriel Mettlach, Alex Sonneborn, Bogachan Sahin, Allen A. Fienberg, Masashi Yanagisawa, James A Bibb, Robert Greene

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Sleep homeostasis reflects a centrally mediated drive for sleep, which increases during waking and resolves during subsequent sleep. Here we demonstrate that mice deficient for glial adenosine kinase (AdK), the primary metabolizing enzyme for adenosine (Ado), exhibit enhanced expression of this homeostatic drive by three independent measures: (1) increased rebound of slow-wave activity; (2) increased consolidation of slow-wave sleep; and (3) increased time constant of slow-wave activity decay during an average slow-wave sleep episode, proposed and validated here as a new index for homeostatic sleep drive. Conversely, mice deficient for the neuronal adenosine A1 receptor exhibit significantly decreased sleep drive as judged by these same indices. Neuronal knock-out of AdK did not influence homeostatic sleep need. Together, these findings implicate a glial-neuronal circuit mediated by intercellular Ado, controlling expression of homeostatic sleep drive. Because AdK is tightly regulated by glial metabolic state, our findings suggest a functional link between cellular metabolism and sleep homeostasis.

Original languageEnglish (US)
Pages (from-to)3709-3721
Number of pages13
JournalJournal of Neuroscience
Issue number13
StatePublished - Mar 30 2016


  • Adenosine
  • Adenosine kinase
  • Delta power
  • Glia
  • SWS
  • Sleep

ASJC Scopus subject areas

  • Neuroscience(all)


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