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PLoS Biol. 2018 Dec 26;16(12):e2006838. doi: 10.1371/journal.pbio.2006838. eCollection 2018 Dec.

An opposing function of paralogs in balancing developmental synapse maturation.

Author information

European Neuroscience Institute Göttingen, University Medical Center, Göttingen, Germany.
Collaborative Research Center 889, University of Göttingen, Göttingen, Germany.
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Systems Neuroscience, Universität Göttingen, Göttingen, Germany.
Department of Psychiatry and Psychotherapy, University Medical Center, Göttingen, Germany.
Department of Neuroanatomy, Medical School, Saarland University, Homburg, Germany.


The disc-large (DLG)-membrane-associated guanylate kinase (MAGUK) family of proteins forms a central signaling hub of the glutamate receptor complex. Among this family, some proteins regulate developmental maturation of glutamatergic synapses, a process vulnerable to aberrations, which may lead to neurodevelopmental disorders. As is typical for paralogs, the DLG-MAGUK proteins postsynaptic density (PSD)-95 and PSD-93 share similar functional domains and were previously thought to regulate glutamatergic synapses similarly. Here, we show that they play opposing roles in glutamatergic synapse maturation. Specifically, PSD-95 promoted, whereas PSD-93 inhibited maturation of immature α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptor (AMPAR)-silent synapses in mouse cortex during development. Furthermore, through experience-dependent regulation of its protein levels, PSD-93 directly inhibited PSD-95's promoting effect on silent synapse maturation in the visual cortex. The concerted function of these two paralogs governed the critical period of juvenile ocular dominance plasticity (jODP), and fine-tuned visual perception during development. In contrast to the silent synapse-based mechanism of adjusting visual perception, visual acuity improved by different mechanisms. Thus, by controlling the pace of silent synapse maturation, the opposing but properly balanced actions of PSD-93 and PSD-95 are essential for fine-tuning cortical networks for receptive field integration during developmental critical periods, and imply aberrations in either direction of this process as potential causes for neurodevelopmental disorders.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have declared that no competing interests exist.

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