| First Author | Liu X | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 14 | Pages | 4483-8 |
| PubMed ID | 25831532 | Mgi Jnum | J:220814 |
| Mgi Id | MGI:5636522 | Doi | 10.1073/pnas.1421758112 |
| Citation | Liu X, et al. (2015) beta-Arrestin-biased signaling mediates memory reconsolidation. Proc Natl Acad Sci U S A 112(14):4483-8 |
| abstractText | A long-standing hypothesis posits that a G protein-coupled signaling pathway mediates beta-adrenergic nervous system functions, including learning and memory. Here we report that memory retrieval (reactivation) induces the activation of beta1-adrenergic beta-arrestin signaling in the brain, which stimulates ERK signaling and protein synthesis, leading to postreactivation memory restabilization. beta-Arrestin2-deficient mice exhibit impaired memory reconsolidation in object recognition, Morris water maze, and cocaine-conditioned place preference paradigms. Postreactivation blockade of both brain beta-adrenergic Gs protein- and beta-arrestin-dependent pathways disrupts memory reconsolidation. Unexpectedly, selective blockade of the Gs/cAMP/PKA signaling but not the beta-arrestin/ERK signaling by the biased beta-adrenergic ligands does not inhibit reconsolidation. Moreover, the expression of beta-arrestin2 in the entorhinal cortex of beta-arrestin 2-deficient mice rescues beta1-adrenergic ERK signaling and reconsolidation in a G protein pathway-independent manner. We demonstrate that beta-arrestin-biased signaling regulates memory reconsolidation and reveal the potential for beta-arrestin-biased ligands in the treatment of memory-related disorders. |
