{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:40:13Z","timestamp":1790023213680,"version":"4.0.1"},"reference-count":154,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Astrocytic calcium signaling is a central mechanism of neuron-glia communication that operates across multiple spatial and temporal scales. Traditionally, research has focused on intracellular Ca2+ oscillations that regulate gliotransmitter release, ion homeostasis, and metabolic support. Recent evidence, however, reveals that extracellular calcium ([Ca2+]o) is not a passive reservoir but a dynamic signaling mediator capable of influencing neuronal excitability within milliseconds. Through mechanisms such as calcium-sensing receptor (CaSR) activation, ion channel modulation, surface charge effects, and ephaptic coupling, astrocytes emerge as active partners in both slow and rapid modes of communication. This dual perspective reshapes our understanding of brain physiology and disease. Disrupted Ca2+ signaling contributes to network instability in epilepsy, synaptic dysfunction in Alzheimer\u2019s and Parkinson\u2019s disease, and impaired maturation in neurodevelopmental disorders. Methodological advances, including Ca2+-selective microelectrodes, genetically encoded extracellular indicators, and computational modeling, are beginning to uncover the richness of extracellular Ca2+ dynamics, though challenges remain in achieving sufficient spatial and temporal resolution. By integrating classical intracellular pathways with emerging insights into extracellular signaling, this review highlights astrocytes as central architects of the ionic landscape. Recognizing calcium as both an intracellular messenger and an extracellular signaling mediator provides a unifying framework for neuron\u2013glia interactions and opens new avenues for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/cells14211709","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Calcium Dynamics in Astrocyte-Neuron Communication from Intracellular to Extracellular Signaling"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5848-8788","authenticated-orcid":false,"given":"Agnieszka","family":"Nowacka","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Nicolas Copernicus University in Toru\u0144, Collegium Medicum in Bydgoszcz, ul. Curie Sk\u0142odowskiej 9, 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"\u015aniegocki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nicolas Copernicus University in Toru\u0144, Collegium Medicum in Bydgoszcz, ul. Curie Sk\u0142odowskiej 9, 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1822-3133","authenticated-orcid":false,"given":"Ewa A.","family":"Zi\u00f3\u0142kowska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1217451","DOI":"10.3389\/fnins.2023.1217451","article-title":"Astrocyte Metabolism and Signaling Pathways in the CNS","volume":"17","author":"Zhang","year":"2023","journal-title":"Front. 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