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Neurexin-2: An inhibitory neurexin that restricts excitatory synapse formation in the hippocampus

Neurexins are widely thought to promote synapse formation and to organize synapse properties. Here we found that in contrast to neurexin-1 and neurexin-3, neurexin-2 unexpectedly restricts synapse formation. In the hippocampus, constitutive or neuron-specific deletions of neurexin-2 nearly doubled t...

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Autores principales: Lin, Pei-Yi, Chen, Lulu Y., Jiang, Man, Trotter, Justin H., Seigneur, Erica, Südhof, Thomas C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821874/
https://www.ncbi.nlm.nih.gov/pubmed/36608123
http://dx.doi.org/10.1126/sciadv.add8856
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author Lin, Pei-Yi
Chen, Lulu Y.
Jiang, Man
Trotter, Justin H.
Seigneur, Erica
Südhof, Thomas C.
author_facet Lin, Pei-Yi
Chen, Lulu Y.
Jiang, Man
Trotter, Justin H.
Seigneur, Erica
Südhof, Thomas C.
author_sort Lin, Pei-Yi
collection PubMed
description Neurexins are widely thought to promote synapse formation and to organize synapse properties. Here we found that in contrast to neurexin-1 and neurexin-3, neurexin-2 unexpectedly restricts synapse formation. In the hippocampus, constitutive or neuron-specific deletions of neurexin-2 nearly doubled the strength of excitatory CA3➔CA1 region synaptic connections and markedly increased their release probability. No effect on inhibitory synapses was detected. Stochastic optical reconstruction microscopy (STORM) superresolution microscopy revealed that the neuron-specific neurexin-2 deletion elevated the density of excitatory CA1 region synapses nearly twofold. Moreover, hippocampal neurexin-2 deletions also increased synaptic connectivity in the CA1 region when induced in mature mice and impaired the cognitive flexibility of spatial memory. Thus, neurexin-2 controls the dynamics of hippocampal synaptic circuits by repressing synapse assembly throughout life, a restrictive function that markedly differs from that of neurexin-1 and neurexin-3 and of other synaptic adhesion molecules, suggesting that neurexins evolutionarily diverged into opposing pro- and antisynaptogenic organizers.
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spelling pubmed-98218742023-01-18 Neurexin-2: An inhibitory neurexin that restricts excitatory synapse formation in the hippocampus Lin, Pei-Yi Chen, Lulu Y. Jiang, Man Trotter, Justin H. Seigneur, Erica Südhof, Thomas C. Sci Adv Neuroscience Neurexins are widely thought to promote synapse formation and to organize synapse properties. Here we found that in contrast to neurexin-1 and neurexin-3, neurexin-2 unexpectedly restricts synapse formation. In the hippocampus, constitutive or neuron-specific deletions of neurexin-2 nearly doubled the strength of excitatory CA3➔CA1 region synaptic connections and markedly increased their release probability. No effect on inhibitory synapses was detected. Stochastic optical reconstruction microscopy (STORM) superresolution microscopy revealed that the neuron-specific neurexin-2 deletion elevated the density of excitatory CA1 region synapses nearly twofold. Moreover, hippocampal neurexin-2 deletions also increased synaptic connectivity in the CA1 region when induced in mature mice and impaired the cognitive flexibility of spatial memory. Thus, neurexin-2 controls the dynamics of hippocampal synaptic circuits by repressing synapse assembly throughout life, a restrictive function that markedly differs from that of neurexin-1 and neurexin-3 and of other synaptic adhesion molecules, suggesting that neurexins evolutionarily diverged into opposing pro- and antisynaptogenic organizers. American Association for the Advancement of Science 2023-01-06 /pmc/articles/PMC9821874/ /pubmed/36608123 http://dx.doi.org/10.1126/sciadv.add8856 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Neuroscience
Lin, Pei-Yi
Chen, Lulu Y.
Jiang, Man
Trotter, Justin H.
Seigneur, Erica
Südhof, Thomas C.
Neurexin-2: An inhibitory neurexin that restricts excitatory synapse formation in the hippocampus
title Neurexin-2: An inhibitory neurexin that restricts excitatory synapse formation in the hippocampus
title_full Neurexin-2: An inhibitory neurexin that restricts excitatory synapse formation in the hippocampus
title_fullStr Neurexin-2: An inhibitory neurexin that restricts excitatory synapse formation in the hippocampus
title_full_unstemmed Neurexin-2: An inhibitory neurexin that restricts excitatory synapse formation in the hippocampus
title_short Neurexin-2: An inhibitory neurexin that restricts excitatory synapse formation in the hippocampus
title_sort neurexin-2: an inhibitory neurexin that restricts excitatory synapse formation in the hippocampus
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821874/
https://www.ncbi.nlm.nih.gov/pubmed/36608123
http://dx.doi.org/10.1126/sciadv.add8856
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