ArticleBiological psychiatry2011
Genetic dissection of behavioral flexibility: reversal learning in mice.
Article in Biological psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 107 citations in OpenAlex.
- Computational modeling of reversal learning impairments in schizophrenia and bipolar disorder reveals shared failure to exploit rewards.Journal of psychopathology and clinical science · 2025Article
- Investigating Motor Coordination Using BXD Recombinant Inbred Mice to Model the Genetic Underpinnings of Developmental Coordination Disorder.Genes, brain, and behavior · 2025Article
- Adolescent-to-adult gains in cognitive flexibility are adaptively supported by reward sensitivity, exploration, and neural variability.Current opinion in behavioral sciences · 2024Article
- Analysis and experimental validation of necroptosis-related molecular classification, immune signature and feature genes in Alzheimer's disease.Apoptosis : an international journal on programmed cell death · 2024Article
- Comparative genomics of widespread and narrow-range white-bellied rats in theZoological research · 2023Article
- Repeatability and heritability of inhibitory control performance in wild toutouwai (Royal Society open science · 2023Article
- Genetic pathways regulating the longitudinal acquisition of cocaine self-administration in a panel of inbred and recombinant inbred mice.Cell reports · 2023Article
- Artificial selection for reversal learning reveals limited repeatability and no heritability of cognitive flexibility in great tits (Proceedings. Biological sciences · 2023Article
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- Dissecting the cross-trait effects of the FOXP2 GWAS hit on clinical and brain phenotypes in adults with ADHD.European archives of psychiatry and clinical neuroscience · 2023Article
- Sex-dependent effects of early life stress on reinforcement learning and limbic cortico-striatal functional connectivity.Neurobiology of stress · 2023Article
- Behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice.Addiction neuroscience · 2022Article
- Extreme phenotypic diversity in operant response to intravenous cocaine or saline infusion in the hybrid mouse diversity panel.Addiction biology · 2022Article
- Heritable variation in locomotion, reward sensitivity and impulsive behaviors in a genetically diverse inbred mouse panel.Genes, brain, and behavior · 2021Article
- Investigating cytosolic 5'-nucleotidase II family genes as candidates for neuropsychiatric disorders in Drosophila (114/150 chr).Translational psychiatry · 2021Article
- Relocation of an Extrasynaptic GABANeuron · 2021Article
- Genetic Modulation of Initial Sensitivity to Δ9-Tetrahydrocannabinol (THC) Among the BXD Family of Mice.Frontiers in genetics · 2021Article
- Metabolic Aspects of Adenosine Functions in the Brain.Frontiers in pharmacology · 2021Review
- Bidirectional causality between addiction and cognitive deficits.International review of neurobiology · 2021Review
- Learning and reaction times in mouse touchscreen tests are differentially impacted by mutations in genes encoding postsynaptic interacting proteins SYNGAP1, NLGN3, DLGAP1, DLGAP2 and SHANK2.Genes, brain, and behavior · 2021Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBehavioral inflexibility is a feature of schizophrenia, attention-deficit/hyperactivity disorder, and behavior addictions that likely results from heritable deficits in the inhibitory control over behavior. Here, we investigate the genetic basis of individual differences in flexibility, measured using an operant reversal learning task.
methodsWe quantified discrimination acquisition and subsequent reversal learning in a cohort of 51 BXD strains of mice (2-5 mice/strain, n = 176) for which we have matched data on sequence, gene expression in key central nervous system regions, and neuroreceptor levels.
resultsStrain variation in trials to criterion on acquisition and reversal was high, with moderate heritability (∼.3). Acquisition and reversal learning phenotypes did not covary at the strain level, suggesting that these traits are effectively under independent genetic control. Reversal performance did covary with dopamine D2 receptor levels in the ventral midbrain, consistent with a similar observed relationship between impulsivity and D2 receptors in humans. Reversal, but not acquisition, is linked to a locus on mouse chromosome 10 with a peak likelihood ratio statistic at 86.2 megabase (p < .05 genome-wide). Variance in messenger RNA levels of select transcripts expressed in neocortex, hippocampus, and striatum correlated with the reversal learning phenotype, including Syn3, Nt5dc3, and Hcfc2.
conclusionsThis work demonstrates the clear trait independence between, and genetic control of, discrimination acquisition and reversal and illustrates how globally coherent data sets for a single panel of highly related strains can be interrogated and integrated to uncover genetic sources and molecular and neuropharmacological candidates of complex behavioral traits relevant to human psychopathology.
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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.