Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo

Norio Takata, Tsuneko Mishima, Chihiro Hisatsune, Terumi Nagai, Etsuko Ebisui, Katsuhiko Mikoshiba, Hajime Hirase

Research output: Contribution to journalArticlepeer-review

297 Citations (Scopus)


Global brain state dynamics regulate plasticity in local cortical circuits, but the underlying cellular and molecular mechanisms are unclear. Here, we demonstrate that astrocyte Ca 2+ signaling provides a critical bridge between cholinergic activation, associated with attention and vigilance states, and somatosensory plasticity in mouse barrel cortex in vivo. We investigated first whether a combined stimulation of mouse whiskers and the nucleus basalis of Meynert (NBM), the principal source of cholinergic innervation to the cortex, leads to enhanced whisker-evoked local field potential. This plasticity is dependent on muscarinic acetylcholine receptors (mAChR) and N-methyl-D-aspartic acid receptors (NMDARs). During the induction of this synaptic plasticity, we find that astrocytic [Ca 2+] i is pronouncedly elevated, which is blocked by mAChR antagonists. The elevation of astrocytic [Ca 2+] i is crucial in this type of synaptic plasticity, as the plasticity could not be induced in inositol-1,4,5-trisphosphate receptor type 2 knock-out (IP 3R2-KO) mice, in which astrocytic [Ca 2+] i surges are diminished. Moreover, NBM stimulation led to a significant increase in the extracellular concentration of the NMDAR coagonist D-serine in wild-type mice when compared to IP 3R2-KO mice. Finally, plasticity in IP 3R2-KO mice could be rescued by externally supplying D-serine. Our data present coherent lines of in vivo evidence for astrocytic involvement in cortical plasticity. These findings suggest an unexpected role of astrocytes as a gate for cholinergic plasticity in the cortex.

Original languageEnglish
Pages (from-to)18155-18165
Number of pages11
JournalJournal of Neuroscience
Issue number49
Publication statusPublished - 2011 Dec 7
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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