TY - JOUR T1 - Astrocyte Calcium Signaling Transforms Cholinergic Modulation to Cortical Plasticity <em>In Vivo</em> JF - The Journal of Neuroscience JO - J. Neurosci. SP - 18155 LP - 18165 DO - 10.1523/JNEUROSCI.5289-11.2011 VL - 31 IS - 49 AU - Norio Takata AU - Tsuneko Mishima AU - Chihiro Hisatsune AU - Terumi Nagai AU - Etsuko Ebisui AU - Katsuhiko Mikoshiba AU - Hajime Hirase Y1 - 2011/12/07 UR - http://www.jneurosci.org/content/31/49/18155.abstract N2 - Global brain state dynamics regulate plasticity in local cortical circuits, but the underlying cellular and molecular mechanisms are unclear. Here, we demonstrate that astrocyte Ca2+ 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 [Ca2+]i is pronouncedly elevated, which is blocked by mAChR antagonists. The elevation of astrocytic [Ca2+]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 (IP3R2-KO) mice, in which astrocytic [Ca2+]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 IP3R2-KO mice. Finally, plasticity in IP3R2-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. ER -