ReviewBiological psychiatry2010
A thalamo-hippocampal-ventral tegmental area loop may produce the positive feedback that underlies the psychotic break in schizophrenia.
Review in Biological psychiatry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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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
68 citing papers in PubMed, 116 citations in OpenAlex.
- Transcutaneous auricular nerve stimulation modulates the functional connectivity of the descending pain modulation system and reward network in patients with chronic low back pain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Trial
- Altered network hub connectivity after acute LSD administration.NeuroImage. Clinical · 2018Trial
- d-Cycloserine augmentation of cognitive remediation in schizophrenia.Schizophrenia research · 2014Trial
- The hippocampus as a generative model.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Paired associates learning performance in rats requires the nucleus reuniens.Behavioral neuroscience · 2026Article
- A causal coding variant regulating alternative splicing ofScience advances · 2026Article
- The thalamic nucleus reuniens orchestrates prefrontal-hippocampal synchrony in memory, emotion, and disease.Frontiers in behavioral neuroscience · 2026Review
- Nucleus Reuniens-Elicited Delta Oscillations Disable the Prefrontal Cortex in Schizophrenia.Cells · 2025Review
- Machine learning for classification of pediatric bipolar disorder with and without psychotic symptoms based on thalamic subregional structural volume.BMC psychiatry · 2025Article
- New Insight into the Mechanism of Neurochemical Imbalance in Multiple Sclerosis: Abnormal Transportation of Brain Extracellular Space.Aging and disease · 2025Article
- The hidden link: Investigating functional connectivity of rarely explored sub-regions of thalamus and superior temporal gyrus in Schizophrenia.Translational neuroscience · 2024Article
- Atypical antipsychotics antagonize GABAMolecular psychiatry · 2023Article
- L-DOPA increases slow-wave sleep duration and selectively modulates memory persistence in older adults.Frontiers in behavioral neuroscience · 2023Article
- Article
- A preclinical study of deep brain stimulation in the ventral tegmental area for alleviating positive psychotic-like behaviors in mice.Frontiers in human neuroscience · 2022Article
- Article
- Cell-type-specific disruption of PERK-eIF2α signaling in dopaminergic neurons alters motor and cognitive function.Molecular psychiatry · 2021Article
- N-methyl-D-aspartate receptor availability in first-episode psychosis: a PET-MR brain imaging study.Translational psychiatry · 2021Article
- Calretinin and calbindin architecture of the midline thalamus associated with prefrontal-hippocampal circuitry.Hippocampus · 2021Article
- Symptomatologic pathomechanism ofEncephalitis (Seoul, Korea) · 2021Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The N-methyl-D-aspartate receptor (NMDAR) hypofunction model of schizophrenia is based on the ability of NMDAR antagonists to produce many symptoms of the disease. Recent work in rats shows that NMDAR antagonist works synergistically with dopamine to produce delta frequency bursting in the thalamus. This finding, together with other results in the literature, suggests a mechanism for the sudden onset of schizophrenia. Among the thalamic nuclei most activated by NMDAR antagonist is the nucleus reuniens. This nucleus excites the cornu ammonis area 1 (CA1) region of the hippocampus. Experiments indicate that such activation can lead to excitation of dopaminergic cells of the ventral tegmental area by a polysynaptic pathway. The resulting elevation of dopamine in the thalamus will enhance thalamic bursting, thereby creating a loop with the potential for positive feedback. We show through computer simulations that in individuals with susceptibility to schizophrenia (e.g., because of partially compromised NMDAR function), an event that stimulates the dopamine system, such as stress, can cause the system to reach the threshold for thalamic bursting. When this occurs, positive feedback in the loop will cause all components to become highly active and to remain active after the triggering stimulus is removed. This is a physiologically specific hypothesis for the sudden and lasting transition that underlies the psychotic break in schizophrenia. Furthermore, the model provides an explanation for the observed selective activation of the CA1 hippocampal region in schizophrenia. The model also predicts an increase of basal activity in the dopamine system and thalamus; the relevant evidence is reviewed.
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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.