Scientific article
Open access

Nitric oxide mediates local activity-dependent excitatory synapse development

Publication date2013

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.

Citation (ISO format)
NIKONENKO, Iryna et al. Nitric oxide mediates local activity-dependent excitatory synapse development. In: Proceedings of the National Academy of Sciences of the United States of America, 2013, vol. 110, n° 44, p. E4142–4151. doi: 10.1073/pnas.1311927110
Main files (1)
Article (Published version)
ISSN of the journal0027-8424

Technical informations

Creation11/19/2013 1:16:00 PM
First validation11/19/2013 1:16:00 PM
Update time03/14/2023 8:56:13 PM
Status update03/14/2023 8:56:13 PM
Last indexation08/29/2023 10:24:40 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack