{"entity": "researcher", "timestamp": "2026-08-22T06:57:50.889Z", "family": "Grant", "given": "Seth G N", "initials": "SGN", "orcid": "0000-0001-8732-8735", "affiliations": ["Genes to Cognition Program, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK. seth.grant@ed.ac.uk.", "Simons Initiative for the Developing Brain (SIDB), Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK. seth.grant@ed.ac.uk."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/323d4b49f8f941a7a12ef77eee7f872e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/323d4b49f8f941a7a12ef77eee7f872e"}}, "publications": [{"entity": "publication", "iuid": "a88a1be2f00a4dadbb1b31facf55137c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a88a1be2f00a4dadbb1b31facf55137c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a88a1be2f00a4dadbb1b31facf55137c"}}, "title": "Developmental disruption and restoration of brain synaptome architecture in the murine Pax6 neurodevelopmental disease model.", "authors": [{"family": "Tomas-Roca", "given": "Laura", "initials": "L"}, {"family": "Qiu", "given": "Zhen", "initials": "Z"}, {"family": "Frans\u00e9n", "given": "Erik", "initials": "E", "orcid": "0000-0003-0281-9450", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8637ab0257cb4d6bbed54277845b7886.json"}}, {"family": "Gokhale", "given": "Ragini", "initials": "R"}, {"family": "Bulovaite", "given": "Edita", "initials": "E"}, {"family": "Price", "given": "David J", "initials": "DJ"}, {"family": "Komiyama", "given": "Noboru H", "initials": "NH"}, {"family": "Grant", "given": "Seth G N", "initials": "SGN", "orcid": "0000-0001-8732-8735", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/323d4b49f8f941a7a12ef77eee7f872e.json"}}], "type": "journal article", "published": "2022-11-11", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "13", "issue": "1", "pages": "6836", "issn-l": "2041-1723"}, "abstract": "Neurodevelopmental disorders of genetic origin delay the acquisition of normal abilities and cause disabling phenotypes. Nevertheless, spontaneous attenuation and even complete amelioration of symptoms in early childhood and adolescence can occur in many disorders, suggesting that brain circuits possess an intrinsic capacity to overcome the deficits arising from some germline mutations. We examined the molecular composition of almost a trillion excitatory synapses on a brain-wide scale between birth and adulthood in mice carrying a mutation in the homeobox transcription factor Pax6, a neurodevelopmental disorder model. Pax6 haploinsufficiency had no impact on total synapse number at any age. By contrast, the molecular composition of excitatory synapses, the postnatal expansion of synapse diversity and the acquisition of normal synaptome architecture were delayed in all brain regions, interfering with networks and electrophysiological simulations of cognitive functions. Specific excitatory synapse types and subtypes were affected in two key developmental age-windows. These phenotypes were reversed within 2-3 weeks of onset, restoring synapse diversity and synaptome architecture to the normal developmental trajectory. Synapse subtypes with rapid protein turnover mediated the synaptome remodeling. This brain-wide capacity for remodeling of synapse molecular composition to recover and maintain the developmental trajectory of synaptome architecture may help confer resilience to neurodevelopmental genetic disorders.", "doi": "10.1038/s41467-022-34131-w", "pmid": "36369219", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9652404"}, {"db": "pii", "key": "10.1038/s41467-022-34131-w"}], "notes": [], "created": "2026-08-21T11:49:11.008Z", "modified": "2026-08-21T11:49:11.114Z"}, {"entity": "publication", "iuid": "d2deb1eba20a40ceb5fa9bc7ed8e392f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d2deb1eba20a40ceb5fa9bc7ed8e392f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d2deb1eba20a40ceb5fa9bc7ed8e392f"}}, "title": "A brainwide atlas of synapses across the mouse life span.", "authors": [{"family": "Cizeron", "given": "M\u00e9lissa", "initials": "M", "orcid": "0000-0002-2124-1917", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/86119983484344fab89a4b42b897ddd4.json"}}, {"family": "Qiu", "given": "Zhen", "initials": "Z", "orcid": "0000-0002-0226-7855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0c92db2c86194dd79ddb8d14de2dd669.json"}}, {"family": "Koniaris", "given": "Babis", "initials": "B", "orcid": "0000-0002-1792-5224", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f8f69ade0b184684a94e3c7a57ec48c3.json"}}, {"family": "Gokhale", "given": "Ragini", "initials": "R"}, {"family": "Komiyama", "given": "Noboru H", "initials": "NH", "orcid": "0000-0001-9960-3597", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c530d669f9fe473595e0119adc2c7a28.json"}}, {"family": "Frans\u00e9n", "given": "Erik", "initials": "E", "orcid": "0000-0003-0281-9450", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8637ab0257cb4d6bbed54277845b7886.json"}}, {"family": "Grant", "given": "Seth G N", "initials": "SGN", "orcid": "0000-0001-8732-8735", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/323d4b49f8f941a7a12ef77eee7f872e.json"}}], "type": "journal article", "published": "2020-07-17", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "369", "issue": "6501", "pages": "270-275", "issn-l": "0036-8075"}, "abstract": "Synapses connect neurons together to form the circuits of the brain, and their molecular composition controls innate and learned behavior. We analyzed the molecular and morphological diversity of 5 billion excitatory synapses at single-synapse resolution across the mouse brain from birth to old age. A continuum of changes alters synapse composition in all brain regions across the life span. Expansion in synapse diversity produces differentiation of brain regions until early adulthood, and compositional changes cause dedifferentiation in old age. The spatiotemporal synaptome architecture of the brain potentially accounts for life-span transitions in intellectual ability, memory, and susceptibility to behavioral disorders.", "doi": "10.1126/science.aba3163", "pmid": "32527927", "labels": [], "xrefs": [{"db": "mid", "key": "EMS86451"}, {"db": "pmc", "key": "PMC7115813"}, {"db": "pii", "key": "science.aba3163"}], "notes": [], "created": "2026-08-21T12:23:17.848Z", "modified": "2026-08-21T12:23:18.073Z"}]}