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Of the three isoforms of IP<jats:sub>3<\/jats:sub> receptors identified in the nervous system, Type 2 (IP<jats:sub>3<\/jats:sub>R2) is the main isoform expressed by astrocytes. The complete lack of IP<jats:sub>3<\/jats:sub>R2 in transgenic mice was shown to significantly disrupt Ca<jats:sup>2+<\/jats:sup> signaling in astrocytes, while leaving neuronal intracellular pathways virtually unperturbed. Whether and how this predominantly nonneuronal receptor might affect long\u2010term memory function has been a matter of intense debate. In this work, we found that the absence of IP<jats:sub>3<\/jats:sub>R2\u2010mediated signaling did not disrupt normal learning or recent (24\u201348\u2009h) memory. Contrary to expectations, however, mice lacking IP<jats:sub>3<\/jats:sub>R2 exhibited remote (2\u20134 weeks) memory deficits. Not only did the lack of IP<jats:sub>3<\/jats:sub>R2 impair remote recognition, fear, and spatial memories, but it also prevented naturally occurring post\u2010encoding memory enhancements consequent to memory consolidation. Consistent with the key role played by the downscaling of synaptic transmission in memory consolidation, we found that NMDAR\u2010dependent long\u2010term depression was abnormal in <jats:italic>ex vivo<\/jats:italic> hippocampal slices acutely prepared from IP<jats:sub>3<\/jats:sub>R2\u2010deficient mice, a deficit that could be prevented upon supplementation with D\u2010serine \u2010 an NMDA\u2010receptor co\u2010agonist whose synthesis depends upon astrocytes' activity. Our results reveal that IP<jats:sub>3<\/jats:sub>R2 activation, which in the brain is paramount for Ca<jats:sup>2+<\/jats:sup> signaling in astrocytes, but not in neurons, can help shape brain plasticity by enhancing the consolidation of newly acquired information into long\u2010term memories that can guide remote cognitive behaviors.<\/jats:p>","DOI":"10.1002\/glia.23679","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T15:05:29Z","timestamp":1564153529000},"page":"1976-1989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Impairments in remote memory caused by the lack of Type 2 IP<sub>3<\/sub> receptors"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2215-7653","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Pinto\u2010Duarte","sequence":"first","affiliation":[{"name":"Computational Neurobiology Laboratory Salk Institute 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