ArticleNature neuroscience2013
Synaptic scaffold evolution generated components of vertebrate cognitive complexity.
Article in Nature neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
150 citing papers in PubMed, 3 syntheses or guidelines pooled it, 263 citations in OpenAlex.
- Touchscreen and Translational Cognition: A Systematic Review of Trials in Humans and Rodents.Journal of neurochemistry · 2025Pooled it
- Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age.Nature communications · 2019Pooled it
- Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review.Journal of psychiatry & neuroscience : JPN · 2018Pooled it
- Molecular and Cellular Mechanisms of Synaptogenesis and Synaptic Refinement During Cerebellar Circuit Formation.International journal of molecular sciences · 2026Review
- A patient-derived mouse model reproduces molecular, neurological, and sleep symptoms of SHINE syndrome.Human molecular genetics · 2026Article
- Article
- GRASPing experience-dependent protein expression signatures enriched for hippocampal engram cell synapses.Science advances · 2026Article
- Differences in Src phosphorylation of PSD-93 and PSD-95 drive differences in scaffolding activity.Protein science : a publication of the Protein Society · 2026Article
- Synapse types are spatially associated with regional hemodynamics in the mouse brain.PLoS biology · 2026Article
- Molecular Physiology of the Neuronal Synapse.Current issues in molecular biology · 2026Review
- Involvement of membrane palmitoylated protein 6 (MPP6) in synapses of mouse cerebrum.Histochemistry and cell biology · 2025Article
- Cross-species translational paradigms for assessing positive valence system as defined by the RDoC matrix.Journal of neurochemistry · 2025Review
- Sequential replacement of PSD95 subunits in postsynaptic supercomplexes is slowest in the cortex.eLife · 2024Article
- Beyond IQ: executive function deficits and their relation to functional, clinical, and neuroimaging outcomes in 3q29 deletion syndrome.Psychological medicine · 2024Article
- Sleep maintains excitatory synapse diversity in the cortex and hippocampus.Current biology : CB · 2024Article
- A mild impairment in reversal learning in a bowl-digging substrate deterministic task but not other cognitive tests in the Dlg2+/- rat model of genetic risk for psychiatric disorder.Genes, brain, and behavior · 2023Article
- Pathway-Based Polygenic Risk Scores for Schizophrenia and Associations With Reported Psychotic-like Experiences and Neuroimaging Phenotypes in the UK Biobank.Biological psychiatry global open science · 2023Article
- Genetic Disruption of System xc-Mediated Glutamate Release from Astrocytes Increases Negative-Outcome Behaviors While Preserving Basic Brain Function in Rat.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Interstrain differences in adolescent fear conditioning after acute alcohol exposure.Brain research bulletin · 2023Article
- Use of an Automated Mouse Touchscreen Platform for Quantification of Cognitive Deficits After Central Nervous System Injury.Methods in molecular biology (Clifton, N.J.) · 2023Article
90 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
The origins and evolution of higher cognitive functions, including complex forms of learning, attention and executive functions, are unknown. A potential mechanism driving the evolution of vertebrate cognition early in the vertebrate lineage (550 million years ago) was genome duplication and subsequent diversification of postsynaptic genes. Here we report, to our knowledge, the first genetic analysis of a vertebrate gene family in cognitive functions measured using computerized touchscreens. Comparison of mice carrying mutations in each of the four Dlg paralogs showed that simple associative learning required Dlg4, whereas Dlg2 and Dlg3 diversified to have opposing functions in complex cognitive processes. Exploiting the translational utility of touchscreens in humans and mice, testing Dlg2 mutations in both species showed that Dlg2's role in complex learning, cognitive flexibility and attention has been highly conserved over 100 million years. Dlg-family mutations underlie psychiatric disorders, suggesting that genome evolution expanded the complexity of vertebrate cognition at the cost of susceptibility to mental illness.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.