Nitric oxide mediates local activity-dependent excitatory synapse development

Nikonenko, I., Nikonenko, A., Mendez, P., Michurina, T. V., Enikolopov, G., Muller, D. (October 2013) Nitric oxide mediates local activity-dependent excitatory synapse development. Proceedings of the National Academy of Sciences of the United States of America, 110 (44). E4142-E4151. ISSN 0027-8424

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DOI: 10.1073/pnas.1311927110


Learning related paradigms play an important role in shaping the development and specificity of synaptic networks, notably by regulating mechanisms of spine growth and pruning. The molecular events underlying these synaptic rearrangements remain poorly understood. Here we identify NO signaling as a key mediator of activity-dependent excitatory synapse development. We find that chronic blockade of NO production in vitro and in vivo interferes with the development of hippocampal and cortical excitatory spine synapses. The effect results from a selective loss of activity-mediated spine growth mechanisms and is associated with morphological and functional alterations of remaining synapses. These effects of NO are mediated by a cGMP cascade and can be reproduced or prevented by postsynaptic expression of vasodilator-stimulated phosphoprotein phospho-mimetic or phospho-resistant mutants. In vivo analyses show that absence of NO prevents the increase in excitatory synapse density induced by environmental enrichment and interferes with the formation of local clusters of excitatory synapses. We conclude that NO plays an important role in regulating the development of excitatory synapses by promoting local activity-dependent spine-growth mechanisms.

Item Type: Paper
Uncontrolled Keywords: synaptic plasticity spinogenesis dendritic spines VASP long-term potentiation environmental enrichment intercellular messenger structural plasticity developing cortex rat hippocampus spine formation in-vivo synthase protein
Subjects: bioinformatics > genomics and proteomics > small molecules > nitric oxide
bioinformatics > genomics and proteomics > small molecules
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > synaptic plasticity
CSHL Authors:
Communities: CSHL labs > Enikopolov lab
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Microscopy Service
Depositing User: Matt Covey
Date: 29 October 2013
Date Deposited: 09 Dec 2013 17:56
Last Modified: 21 Dec 2017 15:38
PMCID: PMC3816470
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