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Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila.

cam.issuedOnline2021-10-13
dc.contributor.authorGiachello, Carlo NG
dc.contributor.authorFan, Yuen Ngan
dc.contributor.authorLandgraf, Matthias
dc.contributor.authorBaines, Richard A
dc.contributor.orcidLandgraf, Matthias [0000-0001-5142-1997]
dc.date.accessioned2021-10-13T15:25:17Z
dc.date.available2021-10-13T15:25:17Z
dc.date.issued2021-10-13
dc.date.submitted2021-07-29
dc.date.updated2021-10-13T15:25:16Z
dc.description.abstractThe emergence of coordinated network function during nervous system development is often associated with critical periods. These phases are sensitive to activity perturbations during, but not outside, of the critical period, that can lead to permanently altered network function for reasons that are not well understood. In particular, the mechanisms that transduce neuronal activity to regulating changes in neuronal physiology or structure are not known. Here, we take advantage of a recently identified invertebrate model for studying critical periods, the Drosophila larval locomotor system. Manipulation of neuronal activity during this critical period is sufficient to increase synaptic excitation and to permanently leave the locomotor network prone to induced seizures. Using genetics and pharmacological manipulations, we identify nitric oxide (NO)-signaling as a key mediator of activity. Transiently increasing or decreasing NO-signaling during the critical period mimics the effects of activity manipulations, causing the same lasting changes in synaptic transmission and susceptibility to seizure induction. Moreover, the effects of increased activity on the developing network are suppressed by concomitant reduction in NO-signaling and enhanced by additional NO-signaling. These data identify NO signaling as a downstream effector, providing new mechanistic insight into how activity during a critical period tunes a developing network.
dc.identifier.doi10.17863/CAM.76807
dc.identifier.eissn2045-2322
dc.identifier.issn2045-2322
dc.identifier.others41598-021-99868-8
dc.identifier.other99868
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329359
dc.languageen
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41598-021-99868-8
dc.subjectAnimals
dc.subjectDrosophila
dc.subjectElectrophysiology
dc.subjectFemale
dc.subjectGene Expression Regulation, Developmental
dc.subjectMice
dc.subjectMotor Neurons
dc.subjectNeuronal Plasticity
dc.subjectNeurons
dc.subjectNitric Oxide
dc.subjectOptogenetics
dc.subjectSignal Transduction
dc.subjectSynaptic Transmission
dc.titleNitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila.
dc.typeArticle
dcterms.dateAccepted2021-09-17
prism.issueIdentifier1
prism.publicationNameSci Rep
prism.volume11
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/R016666/1)
pubs.funder-project-idBBSRC (BB/V014943/1)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41598-021-99868-8

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