| First Author | Pinto-Duarte A | Year | 2019 |
| Journal | Glia | Volume | 67 |
| Issue | 10 | Pages | 1976-1989 |
| PubMed ID | 31348567 | Mgi Jnum | J:279729 |
| Mgi Id | MGI:6343426 | Doi | 10.1002/glia.23679 |
| Citation | Pinto-Duarte A, et al. (2019) Impairments in remote memory caused by the lack of Type 2 IP3 receptors. Glia 67(10):1976-1989 |
| abstractText | The second messenger inositol 1,4,5-trisphosphate (IP3 ) is paramount for signal transduction in biological cells, mediating Ca(2+) release from the endoplasmic reticulum. Of the three isoforms of IP3 receptors identified in the nervous system, Type 2 (IP3 R2) is the main isoform expressed by astrocytes. The complete lack of IP3 R2 in transgenic mice was shown to significantly disrupt Ca(2+) signaling in astrocytes, while leaving neuronal intracellular pathways virtually unperturbed. Whether and how this predominantly nonneuronal receptor might affect long-term memory function has been a matter of intense debate. In this work, we found that the absence of IP3 R2-mediated signaling did not disrupt normal learning or recent (24-48 h) memory. Contrary to expectations, however, mice lacking IP3 R2 exhibited remote (2-4 weeks) memory deficits. Not only did the lack of IP3 R2 impair remote recognition, fear, and spatial memories, but it also prevented naturally occurring post-encoding 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-dependent long-term depression was abnormal in ex vivo hippocampal slices acutely prepared from IP3 R2-deficient mice, a deficit that could be prevented upon supplementation with D-serine - an NMDA-receptor co-agonist whose synthesis depends upon astrocytes' activity. Our results reveal that IP3 R2 activation, which in the brain is paramount for Ca(2+) signaling in astrocytes, but not in neurons, can help shape brain plasticity by enhancing the consolidation of newly acquired information into long-term memories that can guide remote cognitive behaviors. |
