Ligand-independent activity of the ghrelin receptor modulates AMPA receptor trafficking and supports memory formation | Zendy

Luís F. Ribeiro | Zendy; Tatiana Catarino | Zendy; M. Carvalho | Zendy; Luísa Cortes | Zendy; Sandra D. Santos | Zendy; Patricio Opazo | Zendy; Lyn Rosenbrier Ribeiro | Zendy; Bárbara Oliveiros | Zendy; Daniel Choquet | Zendy; José A. Esteban | Zendy; João Peça | Zendy; Ana Luı́sa Carvalho | Zendy

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Ligand-independent activity of the ghrelin receptor modulates AMPA receptor trafficking and supports memory formation

Author(s) -

Luís F. Ribeiro,

Tatiana Catarino,

M. Carvalho,

Luísa Cortes,

Sandra D. Santos,

Patricio Opazo,

Lyn Rosenbrier Ribeiro,

Bárbara Oliveiros,

Daniel Choquet,

José A. Esteban,

João Peça,

Ana Luı́sa Carvalho

Publication year - 2021

Publication title -

science signaling

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.659

H-Index - 154

eISSN - 1937-9145

pISSN - 1945-0877

DOI - 10.1126/scisignal.abb1953

Subject(s) - ghrelin , ampa receptor , receptor , ligand (biochemistry) , microbiology and biotechnology , chemistry , blocking (statistics) , neuroscience , biology , biochemistry , nmda receptor , computer science , computer network

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 Ser 845 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.

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