Editors' ChoiceNeuroscience

Biased memories

Sci. Signal.  14 Apr 2015:
Vol. 8, Issue 372, pp. ec91
DOI: 10.1126/scisignal.aab3265

G protein–coupled receptors (GPCRs) participate in learning and memory. Some GPCRs, such as β1 adrenergic receptors (β1-AR), involved in long-term potentiation (an electrophysiological manifestation of memory) and memory reconsolidation (a process that strengthens and updates memory) can signal through either G proteins or through the arrestin family of adaptors. Liu et al. discovered that mice given the biased β-AR ligands, carvedilol and alprenolol, which function as antagonists of the G protein-mediated pathway and weak agonists of the β-arrestin–mediated pathway, failed to block object recognition memory (ORM) reconsolidation. Mice with a global knockout of β-arrestin2 exhibited impaired memory reconsolidation in ORM, Morris water maze, and cocaine-conditioned place preference experiments. Local viral expression of a fusion between β-arrestin2 and green fluorescent protein (GFP), but not the control protein β-galactosidase-GFP, in entorhinal cortex (a brain region critically involved in ORM) of β-arrestin2-knockout mice rescued the ORM reconsolidation phenotype. Thus, these results indicate that memory reconsolidation involved a G protein–independent β-arrestin2 pathway and suggest that this pathway may have therapeutic potential for treating memory-related disorders.

X. Liu, L. Ma, H. H. Li, B. Huang, Y. X. Li, Y. Z. Tao, L. Ma, β-Arrestin–biased signaling mediates memory reconsolidation. Proc. Natl. Acad. Sci. U.S.A. 112, 4483–4488 (2015). [Abstract] [Full Text]