title: The synaptic proteome during development and plasticity of the mouse visual cortex.
abstract: During brain development, the neocortex shows periods of enhanced plasticity, which enables the acquisition of knowledge and skills that we use and build on in adult life. Key to persistent modifications of neuronal connectivity and plasticity of the neocortex are molecular changes occurring at the synapse. Here we used isobaric tag for relative and absolute quantification to measure levels of 467 synaptic proteins in a well-established model of plasticity in the mouse visual cortex and the regulation of its critical period. We found that inducing visual cortex plasticity by monocular deprivation during the critical period increased levels of kinases and proteins regulating the actin-cytoskeleton and endocytosis. Upon closure of the critical period with age, proteins associated with transmitter vesicle release and the tubulin- and septin-cytoskeletons increased, whereas actin-regulators decreased in line with augmented synapse stability and efficacy. Maintaining the visual cortex in a plastic state by dark rearing mice into adulthood only partially prevented these changes and increased levels of G-proteins and protein kinase A subunits. This suggests that in contrast to the general belief, dark rearing does not simply delay cortical development but may activate signaling pathways that specifically maintain or increase the plasticity potential of the visual cortex. Altogether, this study identified many novel candidate plasticity proteins and signaling pathways that mediate synaptic plasticity during critical developmental periods or restrict it in adulthood.
authors.affiliation: Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Dahlhaus
authors.forename: Ka Wan
authors.initials: KW
authors.lastname: Li
authors.forename: Roel C
authors.initials: RC
authors.lastname: van der Schors
authors.forename: M Hadi
authors.initials: MH
authors.lastname: Saiepour
authors.forename: Pim
authors.initials: P
authors.lastname: van Nierop
authors.forename: J Alexander
authors.initials: JA
authors.lastname: Heimel
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Hermans
authors.forename: Maarten
authors.initials: M
authors.lastname: Loos
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.forename: Christiaan N
authors.initials: CN
authors.lastname: Levelt
mesh_terms: D000367:Age Factors; D000818:Animals; D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D003624:Darkness; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D012683:Sensory Deprivation; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D015349:Vision, Monocular / Q000235:genetics; D014793:Visual Cortex / Q000254:growth & development* / Q000502:physiology*
chemical_list: D002966:Clathrin; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D020543:Proteome