ReviewInternational journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience2011
Prefrontal cortical network connections: key site of vulnerability in stress and schizophrenia.
Review in International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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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
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
- Adverse Life Experiences and Brain Function: A Meta-Analysis of Functional Magnetic Resonance Imaging Findings.JAMA network open · 2023Pooled it
- Effects of clonidine on MMN and P3a amplitude in schizophrenia patients on stable medication.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Trial
- Sex differences in guanfacine effects on drug craving and stress arousal in cocaine-dependent individuals.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Trial
- Early-life medial pulvinar disruption drives schizophrenia-relevant prefrontal inhibitory and cognitive deficits in primates.bioRxiv : the preprint server for biology · 2026Article
- Intrinsic neuronal diversity as a substrate for cortical area specialization in primate vision.Nature communications · 2026Article
- Deficiency of Kif15 impairing synaptic development leads to mood disorder in mice.PLoS genetics · 2025Article
- Peripheral CD4Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- PKC in the perspective of dopamine receptor signaling.Acta biochimica Polonica · 2025Review
- Altered excitatory and inhibitory ionotropic receptor subunit expression in the cortical visuospatial working memory network in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Inhibition of HCN1 currents by norquetiapine, an active metabolite of the atypical anti-psychotic drug quetiapine.Frontiers in pharmacology · 2024Article
- GluN2D Subunit in Parvalbumin Interneurons Regulates Prefrontal Cortex Feedforward Inhibitory Circuit and Molecular Networks Relevant to Schizophrenia.Biological psychiatry · 2023Article
- Chronic academic stress facilitates response inhibition: Behavioral and electrophysiological evidence.Cognitive, affective & behavioral neuroscience · 2022Article
- Impact of COVID-19 Pandemic on Academic Stress and Perceived Classroom Climate in Spanish University Students.International journal of environmental research and public health · 2022Article
- The druggable schizophrenia genome: from repurposing opportunities to unexplored drug targets.NPJ genomic medicine · 2022Review
- Sliding Scale Theory of Attention and Consciousness/Unconsciousness.Behavioral sciences (Basel, Switzerland) · 2022Article
- Direct Regulation of Hyperpolarization-Activated Cyclic-Nucleotide Gated (HCN1) Channels by Cannabinoids.Frontiers in molecular neuroscience · 2022Article
- Impact of Perceived Stress and Immune Status on Decision-Making Abilities during COVID-19 Pandemic Lockdown.Behavioral sciences (Basel, Switzerland) · 2021Article
- Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats.Neuroscience and biobehavioral reviews · 2021Review
- Adolescent stress during, but not after, pubertal onset impairs indices of prepulse inhibition in adult rats.Developmental psychobiology · 2021Article
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
The symptoms of schizophrenia involve profound dysfunction of the prefrontal cortex (PFC). PFC networks create our "mental sketch pad", and PFC dysfunction contributes to symptoms such as cognitive deficits, thought disorder, delusions and hallucinations. Neuropathological studies of schizophrenia have shown marked loss of dendritic spines in deep layer III, the sublayer where PFC microcircuits reside. The microcircuits consist of recurrent excitatory pyramidal cell networks that interconnect on spines, and excite each other via NMDA receptor signaling. The pyramidal cell persistent firing is sculpted by lateral inhibition from GABAergic basket and chandelier cells, thus creating tuned, persistent firing needed for accurate representational knowledge (i.e., working memory). The strength of pyramidal cell network connections is markedly and flexibly altered by intracellular signaling pathways in dendritic spines, a process called dynamic network connectivity (DNC). DNC proteins such as HCN channels are concentrated on dendritic spines in deep layer III. Under optimal conditions, network inputs to pyramidal cells are strengthened by noradrenergic alpha-2A inhibition of cAMP-HCN channel signaling, and sculpted by dopamine D1-cAMP-HCN channel weakening of inappropriate inputs. However, with stress exposure, high levels of cAMP-HCN channel signaling produces a collapse in network firing. With chronic stress exposure, spines reduce in size and are lost, and this process involves increased PKC signaling. Importantly, molecules that normally strengthen PFC networks connections and/or reverse the stress response, are often genetically altered in schizophrenia. As exposure to stress is a key factor in the precipitation of schizophrenic symptoms, these dysregulated signaling pathways in deep layer III may interact with already vulnerable circuitry to cause spine loss and the descent into illness.
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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.