PXD004537

PXD004537 is an original dataset announced via ProteomeXchange.

Title	Homer1a drives Homeostatic Scaling-down of Excitatory Synapses During Sleep
Description	Homeostatic scaling is a global form of synaptic plasticity used by neurons to adjust overall synaptic weight and maintain neuronal firing rates while protecting information coding. While homeostatic scaling has been demonstrated in vitro, a clear physiological function of this plasticity type has not been defined. Sleep is an essential process that modifies synapses to support cognitive functions such as learning and memory. Evidence suggests that information coding during wake drives synapse strengthening which is offset by weakening of synapses during sleep .Here we use biochemical fractionation, proteomics and in vivo two-photon imaging to characterize wide-spread changes in synapse composition in mice through the wake/sleep cycle. We find that during the sleep phase, synapses are weakened through dephosphorylation and removal of synaptic AMPA-type glutamate receptors (AMPARs) driven by the immediate early gene Homer1a and signaling from group I metabotropic glutamate receptors (mGluR1/5), consistent with known mechanisms of homeostatic scaling-down in vitro. Further, we find that these changes are important in the consolidation of contextual memories. While Homer1a gene expression is driven by neuronal activity during wake, Homer1a protein targeting to synapses serves as an integrator of arousal and sleep need through signaling by the wake-promoting neuromodulator noradrenaline (NA) and sleep-promoting modulator adenosine. During sleep or periods of increased sleep need Homer1a enters synapses where it remodels mGluR1/5 signaling complexes to promote AMPAR removal. Thus, we have characterized widespread changes occurring at synapses through the wake/sleep cycle and demonstrated that known mechanisms of homeostatic scaling-down previously demonstrated only in vitro are active in the brain during sleep to remodel synapses, contributing to memory consolidation.
HostingRepository	PRIDE
AnnounceDate	2017-02-13
AnnouncementXML	Submission_2017-02-13_03:22:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard Huganir
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2016-07-11 01:34:23	ID requested
⏵ 1	2017-02-13 03:22:42	announced

Diering GH, Nirujogi RS, Roth RH, Worley PF, Pandey A, Huganir RL, Homer1a drives homeostatic scaling-down of excitatory synapses during sleep. Science, 355(6324):511-515(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Sleep, Homer1A, Phosphoproteomics

Richard L. Huganir
contact affiliation	Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
contact email	rhuganir@jhmi.edu
lab head
Richard Huganir
contact affiliation	Johns Hopkins University
contact email	rhuganir@jhmi.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004537
     1. Label: PRIDE project
     2. Name: Homer1a drives Homeostatic Scaling-down of Excitatory Synapses During Sleep