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Title: Ligand-independent activity of the ghrelin receptor modulates AMPA receptor trafficking and supports memory formation
Authors: Ribeiro, Luís F.
Catarino, Tatiana 
Carvalho, Mário
Cortes, Luísa 
Santos, Sandra D.
Opazo, Patricio O.
Ribeiro, Lyn Rosenbrier
Oliveiros, Bárbara
Choquet, Daniel
Esteban, José A. 
Peça, João 
Carvalho, Ana Luísa 
Issue Date: 2021
Publisher: American Association for the Advancement of Science
Project: IF/00812/2012 
CENTRO-01-0145-FEDER0000088: BrainHealth 2020 
Serial title, monograph or event: Science Signaling
Volume: 14
Issue: 670
Abstract: The biological signals of hunger, satiety, and memory are interconnected. The role of the hormone ghrelin in regulating feeding and memory makes ghrelin receptors attractive targets for associated disorders. We investigated the effects of the high ligand-independent activity of the ghrelin receptor GHS-R1a on the physiology of excitatory synapses in the hippocampus. Blocking this activity produced a decrease in the synaptic content of AMPA receptors in hippocampal neurons and a reduction in GluA1 phosphorylation at Ser845. Reducing the ligand-independent activity of GHS-R1a increased the surface diffusion of AMPA receptors and impaired AMPA receptor–dependent synaptic delivery induced by chemical long-term potentiation. Accordingly, we found that blocking this GHS-R1a activity impaired spatial and recognition memory in mice. These observations support a role for the ligand-independent activity of GHS-R1a in regulating AMPA receptor trafficking under basal conditions and in the context of synaptic plasticity that underlies learning.
ISSN: 1945-0877
DOI: 10.1126/scisignal.abb1953
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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