?-Arrestin-biased signaling mediates memory reconsolidation.

ABSTRACT: A long-standing hypothesis posits that a G protein-coupled signaling pathway mediates ?-adrenergic nervous system functions, including learning and memory. Here we report that memory retrieval (reactivation) induces the activation of ?1-adrenergic ?-arrestin signaling in the brain, which stimulates ERK signaling and protein synthesis, leading to postreactivation memory restabilization. ?-Arrestin2-deficient mice exhibit impaired memory reconsolidation in object recognition, Morris water maze, and cocaine-conditioned place preference paradigms. Postreactivation blockade of both brain ?-adrenergic Gs protein- and ?-arrestin-dependent pathways disrupts memory reconsolidation. Unexpectedly, selective blockade of the Gs/cAMP/PKA signaling but not the ?-arrestin/ERK signaling by the biased ?-adrenergic ligands does not inhibit reconsolidation. Moreover, the expression of ?-arrestin2 in the entorhinal cortex of ?-arrestin 2-deficient mice rescues ?1-adrenergic ERK signaling and reconsolidation in a G protein pathway-independent manner. We demonstrate that ?-arrestin-biased signaling regulates memory reconsolidation and reveal the potential for ?-arrestin-biased ligands in the treatment of memory-related disorders.

SUBMITTER: Liu X 

PROVIDER: S-EPMC4394255 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other