ArticleSchizophrenia research2013
Frontal cortical synaptic communication is abnormal in Disc1 genetic mouse models of schizophrenia.
Article in Schizophrenia research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Histamine HProceedings of the National Academy of Sciences of the United States of America · 2023Article
- DISC1 and reelin interact to alter cognition, inhibition, and neurogenesis in a novel mouse model of schizophrenia.Frontiers in cellular neuroscience · 2023Article
- Astrocyte Bioenergetics and Major Psychiatric Disorders.Advances in neurobiology · 2021Review
- Effect of Neonatal Treatment With the NMDA Receptor Antagonist, MK-801, During Different Temporal Windows of Postnatal Period in Adult Prefrontal Cortical and Hippocampal Function.Frontiers in behavioral neuroscience · 2021Article
- Adolescent psychosocial stress enhances sensitization to cocaine exposure in genetically vulnerable mice.Neuroscience research · 2020Article
- An Overview of Animal Models Related to Schizophrenia.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2019Review
- Dominant-Negative DISC1 Alters the Dopaminergic Modulation of Inhibitory Interneurons in the Mouse Prefrontal Cortex.Molecular neuropsychiatry · 2018Article
- Adolescent stress leads to glutamatergic disturbance through dopaminergic abnormalities in the prefrontal cortex of genetically vulnerable mice.Psychopharmacology · 2017Article
- Expression of mutant DISC1 in Purkinje cells increases their spontaneous activity and impairs cognitive and social behaviors in mice.Neurobiology of disease · 2017Article
- Epistatic and Independent Effects on Schizophrenia-Related Phenotypes Following Co-disruption of the Risk Factors Neuregulin-1 × DISC1.Schizophrenia bulletin · 2017Article
- Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro.Translational psychiatry · 2016Article
- Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1.Translational psychiatry · 2015Article
- Neurophysiological modification of CA1 pyramidal neurons in a transgenic mouse expressing a truncated form of disrupted-in-schizophrenia 1.The European journal of neuroscience · 2014Article
- Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system.The European journal of neuroscience · 2014Review
- Glutamatergic postsynaptic density protein dysfunctions in synaptic plasticity and dendritic spines morphology: relevance to schizophrenia and other behavioral disorders pathophysiology, and implications for novel therapeutic approaches.Molecular neurobiology · 2014Review
- Article
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
Mouse models carrying Disc1 mutations may provide insights into how Disc1 genetic variations contribute to schizophrenia (SZ) susceptibility. Disc1 mutant mice show behavioral and cognitive disturbances reminiscent of SZ. To dissect the synaptic mechanisms underlying these phenotypes, we examined electrophysiological properties of cortical neurons from two mouse models, the first expressing a truncated mouse Disc1 (mDisc1) protein throughout the entire brain, and the second expressing a truncated human Disc1 (hDisc1) protein in forebrain regions. We obtained whole-cell patch clamp recordings to examine how altered expression of Disc1 protein changes excitatory and inhibitory synaptic transmissions onto cortical pyramidal neurons in the medial prefrontal cortex in 4-7 month-old mDisc1 and hDisc1 mice. In both mDisc1 and hDisc1 mice, the frequency of spontaneous EPSCs was greater than in wild-type littermate controls. Male mice from both lines were more affected by the Disc1 mutation than were females, exhibiting increases in the ratio of excitatory to inhibitory events. Changes in spontaneous IPSCs were only observed in the mDisc1 model and were sex-specific, with diminished cortical GABAergic neurotransmission, a well-documented characteristic of SZ, occurring only in male mDisc1 mice. In contrast, female mDisc1 mice showed an increase in the frequency of small-amplitude sIPSCs. These findings indicate that truncations of Disc1 alter glutamatergic and GABAergic neurotransmission both commonly and differently in the models and some of the effects are sex-specific, revealing how altered Disc1 expression may contribute to behavioral disruptions and cognitive deficits of SZ.
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Registered trials
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