ArticleTranslational psychiatry2016
Knockout of NMDA-receptors from parvalbumin interneurons sensitizes to schizophrenia-related deficits induced by MK-801.
Article in Translational psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment.Molecular psychiatry · 2023Pooled it
- NMDA receptor ablation in medial prefrontal cortex disrupts value updating and reward history integration.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- 16p11.2 duplication and NMDA receptor antagonism have distinct impacts on reward learning and decision making.Psychopharmacology · 2026Article
- Hippocampal transcriptome profiling in a 22q11.2 deletion syndrome mouse model: comparison with human schizophrenia.Molecular brain · 2026Article
- Comprehensive Assessment of Druggable Targets in Cortical Neurons Reveals Biological Limits of Cell Type-Specific Neuropharmacology.Biomedicines · 2026Article
- The GluA1 cytoplasmic tail regulates intracellular AMPA receptor trafficking and synaptic transmission onto dentate gyrus GABAergic interneurons, gating response to novelty.Molecular psychiatry · 2026Article
- Was Kraepelin Prescient Regarding Excitation-Inhibition Imbalance in Schizophrenia?Schizophrenia bulletin open · 2026Article
- Schizophrenia Pathophysiology: Neurotransmitter Dysfunctions and Biomarker Frontiers.Current topics in medicinal chemistry · 2026Review
- 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
- Discovering functional interactions among schizophrenia-risk genes by combining behavioral genetics with cell biology.Neuroscience and biobehavioral reviews · 2024Review
- Advances in the Treatment of Cognitive Impairment in Schizophrenia: Targeting NMDA Receptor Pathways.International journal of molecular sciences · 2024Review
- The excitatory-inhibitory balance as a target for the development of novel drugs to treat schizophrenia.Biochemical pharmacology · 2024Review
- Generation of Rare Human NMDA Receptor Variants in Mice.Methods in molecular biology (Clifton, N.J.) · 2024Article
- D-serine reconstitutes synaptic and intrinsic inhibitory control of pyramidal neurons in a neurodevelopmental mouse model for schizophrenia.Nature communications · 2023Article
- Striatum-projecting prefrontal cortex neurons support working memory maintenance.Nature communications · 2023Article
- GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia.Molecular psychiatry · 2023Review
- GluN2D Subunit in Parvalbumin Interneurons Regulates Prefrontal Cortex Feedforward Inhibitory Circuit and Molecular Networks Relevant to Schizophrenia.Biological psychiatry · 2023Article
- Dual orexin/hypocretin receptor antagonism attenuates NMDA receptor hypofunction-induced attentional impairments in a rat model of schizophrenia.Behavioural brain research · 2023Article
- Potential Roles for the GluN2D NMDA Receptor Subunit in Schizophrenia.International journal of molecular sciences · 2023Review
- Btbd11 supports cell-type-specific synaptic function.Cell reports · 2023Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
It has been suggested that a functional deficit in NMDA-receptors (NMDARs) on parvalbumin (PV)-positive interneurons (PV-NMDARs) is central to the pathophysiology of schizophrenia. Supportive evidence come from examination of genetically modified mice where the obligatory NMDAR-subunit GluN1 (also known as NR1) has been deleted from PV interneurons by Cre-mediated knockout of the corresponding gene Grin1 (Grin1(ΔPV) mice). Notably, such PV-specific GluN1 ablation has been reported to blunt the induction of hyperlocomotion (a surrogate for psychosis) by pharmacological NMDAR blockade with the non-competitive antagonist MK-801. This suggests PV-NMDARs as the site of the psychosis-inducing action of MK-801. In contrast to this hypothesis, we show here that Grin1(ΔPV) mice are not protected against the effects of MK-801, but are in fact sensitized to many of them. Compared with control animals, Grin1(ΔPV)mice injected with MK-801 show increased stereotypy and pronounced catalepsy, which confound the locomotor readout. Furthermore, in Grin1(ΔPV)mice, MK-801 induced medial-prefrontal delta (4 Hz) oscillations, and impaired performance on tests of motor coordination, working memory and sucrose preference, even at lower doses than in wild-type controls. We also found that untreated Grin1(ΔPV)mice are largely normal across a wide range of cognitive functions, including attention, cognitive flexibility and various forms of short-term memory. Taken together these results argue against PV-specific NMDAR hypofunction as a key starting point of schizophrenia pathophysiology, but support a model where NMDAR hypofunction in multiple cell types contribute to the disease.
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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.