Convergence of adenosine and GABA signaling for synapse stabilization during development.

Ferran Gomez-Castro, Stefania Zappettini, Jessica C. Pressey, Carla G. Silva, Marion Russeau, Nicolas Gervasi, Marta Figueiredo, Claire Montmasson, Marianne Renner, Paula M. Canas, Francisco Q. Gonçalves, Sofia Alçada-Morais, Eszter Szabó, Ricardo J. Rodrigues, Paula Agostinho, Angelo R. Tomé, Ghislaine Caillol, Olivier Thoumine, Xavier Nicol, Christophe Leterrier, Rafael Lujan, Shiva K. Tyagarajan, Rodrigo A. Cunha, Monique Esclapez, Christophe Bernard, Sabine Lévi
Science. 2021-11-05; 374(6568):
DOI: 10.1126/science.abk2055


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Synapse stabilization

Early in brain development, neurons connect to each other enthusiastically. With development, an overabundance of synapses is winnowed down to refine efficiently connected circuits. Inactive synapses are prime targets for elimination, whereas active synapses tend to be retained. Gomez-Castro
et al
. took a closer look at how those choices are made (see the Perspective by Blum and Lopes). When postsynaptic adenosine receptors are muted or do not find enough extracellular adenosine, synapses get eliminated. Neurotransmitter-dependent signaling pathways drive protein kinase A to phosphorylate the postsynaptic scaffolding molecule gephyrin. Together with a partner synaptogenic membrane protein, gephyrin is required for the stabilization of γ-aminobutyric acid receptors. Adenosine receptors thus detect synaptic activity and in turn drive the stabilization of synapses that produce such activity. —PJH

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