ReviewBiological psychiatry2022
Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia.
Review in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Schizophrenia: Converging Neurobiological Mechanisms and Emerging Therapeutic Strategies.Biomolecules · 2026Review
- Dorsolateral Prefrontal Cortex Circuitry at the Intersection of Cognition and Disease.Biological psychiatry · 2026Review
- Gα13 Overexpression in the Medial Prefrontal Cortex Disrupts Social Behavior Through the Adcyap1/cAMP/PKA/NMDAR Pathway.Schizophrenia bulletin · 2026Article
- AugGCL: Multimodal graph learning for spatial transcriptomics analysis with enhanced gene and morphological data.PLoS computational biology · 2026Article
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Selective magnetic stimulation downregulates the GABAMolecular psychiatry · 2026Article
- Unraveling the mysteries of schizophrenia: Insights into prefrontal cortex dysfunction and therapeutic implications.World journal of psychiatry · 2025Review
- Somatostatin and its receptors involvement in sevoflurane-induced neurotoxicity: a narrative review.BMC anesthesiology · 2025Review
- Brain region and sex differences in human microglia morphology and function.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Stress and Inflammation Target Dorsolateral Prefrontal Cortex Function: Neural Mechanisms Underlying Weakened Cognitive Control.Biological psychiatry · 2025Review
- Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Neuropsychiatric Manifestations of COVID-19 Disease and Post COVID Syndrome: The Role of N-acetylcysteine and Acetyl-L-carnitine.Current neuropharmacology · 2025Review
- Complement and microglia activation mediate stress-induced synapse loss in layer 2/3 of the medial prefrontal cortex in male mice.Nature communications · 2024Article
- Characterizing the Most Vulnerable Prefrontal Cortical Neurons in Schizophrenia.The American journal of psychiatry · 2024Article
- Identifying plasma metabolic characteristics of major depressive disorder, bipolar disorder, and schizophrenia in adolescents.Translational psychiatry · 2024Article
- stMMR: accurate and robust spatial domain identification from spatially resolved transcriptomics with multimodal feature representation.GigaScience · 2024Article
- Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer's disease.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- A critical period plasticity framework for the sensorimotor-association axis of cortical neurodevelopment.Trends in neurosciences · 2023Review
- SiGra: single-cell spatial elucidation through an image-augmented graph transformer.Nature communications · 2023Article
- Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID.Neurology international · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Schizophrenia is associated with reduced numbers of spines and dendrites from layer III of the dorsolateral prefrontal cortex (dlPFC), the layer that houses the recurrent excitatory microcircuits that subserve working memory and abstract thought. Why are these synapses so vulnerable, while synapses in deeper or more superficial layers are little affected? This review describes the special molecular properties that govern layer III neurotransmission and neuromodulation in the primate dlPFC and how they may render these circuits particularly vulnerable to genetic and environmental insults. These properties include a reliance on NMDA receptor rather than AMPA receptor neurotransmission; cAMP (cyclic adenosine monophosphate) magnification of calcium signaling near the glutamatergic synapse of dendritic spines; and potassium channels opened by cAMP/PKA (protein kinase A) signaling that dynamically alter network strength, with built-in mechanisms to take dlPFC "offline" during stress. A variety of genetic and/or environmental insults can lead to the same phenotype of weakened layer III connectivity, in which mechanisms that normally strengthen connectivity are impaired and those that normally weaken connectivity are intensified. Inflammatory mechanisms, such as increased kynurenic acid and glutamate carboxypeptidase II expression, are especially detrimental to layer III dlPFC neurotransmission and modulation, mimicking genetic insults. The combination of genetic and inflammatory insults may cross the threshold into pathology.
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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.