ArticleMolecular psychiatry2018
Male-specific deficits in natural reward learning in a mouse model of neurodevelopmental disorders.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Emerging behavioral and neuroimaging biomarkers for early and accurate characterization of autism spectrum disorders: a systematic review.Translational psychiatry · 2021Pooled it
- The functional neural architecture of dysfunctional reward processing in autism.NeuroImage. Clinical · 2021Pooled it
- Complement contributes to hyperactive behavior in the 16p11.2 hemideletion mouse model.Brain, behavior, and immunity · 2026Article
- Fibrinogen as a Driver of Oxidative Stress and Apoptosis in the Fetal Brain After Maternal Influenza.Research square · 2026Article
- 16p11.2 duplication and NMDA receptor antagonism have distinct impacts on reward learning and decision making.Psychopharmacology · 2026Article
- A chromosome region linked to neurodevelopmental disorders influences locomotor behavior through sex-specific neural circuits.Nature communications · 2026Article
- 16p11.2 duplication shows early male-biased impacts on reward learning, but NMDA receptor antagonism reduces optimal choice selection in both wildtypes and 16p11.2 duplication.bioRxiv : the preprint server for biology · 2025Article
- Genetic changes linked to two different syndromic forms of autism enhance reinforcement learning in early adolescent male but not female mice.bioRxiv : the preprint server for biology · 2025Article
- Control of striatal circuit development by the chromatin regulatorScience advances · 2025Article
- Sex differences in morphine sensitivity of neuroligin-3 knockout mice.Psychopharmacology · 2024Article
- The pleiotropic spectrum of proximal 16p11.2 CNVs.American journal of human genetics · 2024Review
- Sex mechanisms as nonbinary influences on cognitive diversity.Hormones and behavior · 2024Review
- Dissecting 16p11.2 hemi-deletion to study sex-specific striatal phenotypes of neurodevelopmental disorders.Molecular psychiatry · 2024Article
- Developmental Disruptions of the Dorsal Striatum in Autism Spectrum Disorder.Biological psychiatry · 2024Review
- Understanding copy number variations through their genes: a molecular view on 16p11.2 deletion and duplication syndromes.Frontiers in pharmacology · 2024Review
- DREADD activation of the lateral orbitofrontal increases cocaine-taking and cocaine-seeking in male and female rats during intermittent access self-administration under risky conditions.Addiction neuroscience · 2023Article
- Dissecting the autism-associated 16p11.2 locus identifies multiple drivers in neuroanatomical phenotypes and unveils a male-specific role for the major vault protein.Genome biology · 2023Article
- Critical periods and Autism Spectrum Disorders, a role for sleep.Neurobiology of sleep and circadian rhythms · 2023Article
- Sleep disturbances in autism spectrum disorder: Animal models, neural mechanisms, and therapeutics.Neurobiology of sleep and circadian rhythms · 2023Review
- Chemogenetic rectification of the inhibitory tone onto hippocampal neurons reverts autistic-like traits and normalizes local expression of estrogen receptors in the Ambra1+/- mouse model of female autism.Translational psychiatry · 2023Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Neurodevelopmental disorders, including autism spectrum disorders, are highly male biased, but the underpinnings of this are unknown. Striatal dysfunction has been strongly implicated in the pathophysiology of neurodevelopmental disorders, raising the question of whether there are sex differences in how the striatum is impacted by genetic risk factors linked to neurodevelopmental disorders. Here we report male-specific deficits in striatal function important to reward learning in a mouse model of 16p11.2 hemideletion, a genetic mutation that is strongly associated with the risk of neurodevelopmental disorders, particularly autism and attention-deficit hyperactivity disorder. We find that male, but not female, 16p11.2 deletion animals show impairments in reward-directed learning and maintaining motivation to work for rewards. Male, but not female, deletion animals overexpress mRNA for dopamine receptor 2 and adenosine receptor 2a in the striatum, markers of medium spiny neurons signaling via the indirect pathway, associated with behavioral inhibition. Both sexes show a 50% reduction of mRNA levels of the genes located within the 16p11.2 region in the striatum, including the kinase extracellular-signal related kinase 1 (ERK1). However, hemideletion males show increased activation in the striatum for ERK1, both at baseline and in response to sucrose, a signaling change associated with decreased striatal plasticity. This increase in ERK1 phosphorylation is coupled with a decrease in the abundance of the ERK phosphatase striatum-enriched protein-tyrosine phosphatase in hemideletion males. In contrast, females do not show activation of ERK1 in response to sucrose, but notably hemideletion females show elevated protein levels for ERK1 as well as the related kinase ERK2 over what would be predicted by mRNA levels. These data indicate profound sex differences in the impact of a genetic lesion linked with neurodevelopmental disorders, including mechanisms of male-specific vulnerability and female-specific resilience impacting intracellular signaling in the brain.
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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.