ArticleMolecular psychiatry2020
Reduced GluN1 in mouse dentate gyrus is associated with CA3 hyperactivity and psychosis-like behaviors.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Schizophrenia.Nature reviews. Disease primers · 2025Review
- Hippocampal subfield activity in schizophrenia: Effects of the disease course.Schizophrenia research · 2025Article
- Article
- Pharmacological reduction of reverse-translated hippocampal hyperactivity in mouse: relevance for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- An increased copy number of glycine decarboxylase (GLDC) associated with psychosis reduces extracellular glycine and impairs NMDA receptor function.Molecular psychiatry · 2025Article
- Glutamatergic dysfunction leads to a hyper-dopaminergic phenotype through deficits in short-term habituation: a mechanism for aberrant salience.Molecular psychiatry · 2023Article
- A missense mutation inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models.International journal of molecular sciences · 2022Review
- Disrupted mossy fiber connections from defective embryonic neurogenesis contribute to SOX11-associated schizophrenia.Cellular and molecular life sciences : CMLS · 2022Article
- Linking proteomic alterations in schizophrenia hippocampus to NMDAr hypofunction in human neurons and oligodendrocytes.European archives of psychiatry and clinical neuroscience · 2021Article
- Transgenic modeling of Ndr2 gene amplification reveals disturbance of hippocampus circuitry and function.iScience · 2021Article
- Hippocampal subfield transcriptome analysis in schizophrenia psychosis.Molecular psychiatry · 2021Article
- Using internal memory representations in associative learning to study hallucination-like phenomenon.Neurobiology of learning and memory · 2020Review
- In silico hippocampal modeling for multi-target pharmacotherapy in schizophrenia.NPJ schizophrenia · 2020Article
- Associating Psychotic Symptoms with Altered Brain Anatomy in Psychotic Disorders Using Multidimensional Item Response Theory Models.Cerebral cortex (New York, N.Y. : 1991) · 2020Article
- Effects of genetic and environmental risk for schizophrenia on hippocampal activity and psychosis-like behavior in mice.Behavioural brain research · 2018Article
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10 authors at 2 institutions in 2 countries.
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Abstract
Recent findings from in vivo-imaging and human post-mortem tissue studies in schizophrenic psychosis (SzP), have demonstrated functional and molecular changes in hippocampal subfields that can be associated with hippocampal hyperexcitability. In this study, we used a subfield-specific GluN1 knockout mouse with a disease-like molecular perturbation expressed only in hippocampal dentate gyrus (DG) and assessed its association with hippocampal physiology and psychosis-like behaviors. First, we used whole-cell patch-clamp recordings to measure the physiological changes in hippocampal subfields and cFos immunohistochemistry to examine cellular excitability. DG-GluN1 KO mice show CA3 cellular hyperactivity, detected using two approaches: (1) increased excitatory glutamate transmission at mossy fibers (MF)-CA3 synapses, and (2) an increased number of cFos-activated pyramidal neurons in CA3, an outcome that appears to project downstream to CA1 and basolateral amygdala (BLA). Furthermore, we examined psychosis-like behaviors and pathological memory processing; these show an increase in fear conditioning (FC), a reduction in prepulse inhibition (PPI) in the KO animal, along with a deterioration in memory accuracy with Morris Water Maze (MWM) and reduced social memory (SM). Moreover, with DREADD vectors, we demonstrate a remarkably similar behavioral profile when we induce CA3 hyperactivity. These hippocampal subfield changes could provide the basis for the observed increase in human hippocampal activity in SzP, based on the shared DG-specific GluN1 reduction. With further characterization, these animal model systems may serve as targets to test psychosis mechanisms related to hippocampus and assess potential hippocampus-directed treatments.
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