ReviewFrontiers in pharmacology2020
Hippocampal Hyperactivity as a Druggable Circuit-Level Origin of Aberrant Salience in Schizophrenia.
Review in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Brain functional connectivity patterns associated with adiposity in schizophrenia.Psychiatry research. Neuroimaging · 2026Article
- Antipsychotic Drug Action, Novel Treatment Targets, and the Failure of Current Clinical Trial Designs in Evaluating New Target Molecules.Biological psychiatry · 2026Review
- Novel positive allosteric modulators of alpha 5 subunit-containing GABASchizophrenia research · 2026Article
- Comprehensive Assessment of Druggable Targets in Cortical Neurons Reveals Biological Limits of Cell Type-Specific Neuropharmacology.Biomedicines · 2026Article
- Prefrontal Cortex Dysfunction as a Precipitating Factor for Schizophrenia and Depression.Journal of neurochemistry · 2026Review
- Excitability-margin narrowing as a candidate gating mechanism for maladaptive circuit reactivation: a ventral CA1-centered model.Frontiers in behavioral neuroscience · 2026Article
- Too Little and Too Much: Balanced Hippocampal, But Not Medial Prefrontal, Neural Activity Is Required for Intact Novel Object Recognition in Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Serotonin Modulation of Dorsoventral Hippocampus in Physiology and Schizophrenia.International journal of molecular sciences · 2025Review
- Pharmacological reduction of reverse-translated hippocampal hyperactivity in mouse: relevance for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- MRI Study of the Brain Structural Characteristic in Persecutory Delusions.Bulletin of experimental biology and medicine · 2025Article
- Acute optogenetic induction of the prodromal endophenotype of CA1 hyperactivity causes schizophrenia-related deficits in cognition and salience attribution.Schizophrenia (Heidelberg, Germany) · 2024Article
- The excitatory-inhibitory balance as a target for the development of novel drugs to treat schizophrenia.Biochemical pharmacology · 2024Review
- Aberrant salience in acute versus chronic schizophrenia: Do medication and positive symptoms make a difference?Indian journal of psychiatry · 2024Article
- Correlation between desynchrony of hippocampal neural activity and hyperlocomotion in the model mice of schizophrenia and therapeutic effects of aripiprazole.CNS neuroscience & therapeutics · 2024Article
- The contributions of neonatal inhalation of copper to air pollution-induced neurodevelopmental outcomes in mice.Neurotoxicology · 2024Article
- Aberrant intra- and internetwork functional connectivity patterns of the anterior and posterior hippocampal networks in schizophrenia.CNS neuroscience & therapeutics · 2023Article
- Levetiracetam Attenuates Adolescent Stress-induced Behavioral and Electrophysiological Changes Associated With Schizophrenia in Adult Rats.Schizophrenia bulletin · 2023Article
- Aberrant salience in cannabis-induced psychosis: a comparative study.Frontiers in psychiatry · 2023Article
- Relevance of interactions between dopamine and glutamate neurotransmission in schizophrenia.Molecular psychiatry · 2022Review
- Latent inhibition, aberrant salience, and schizotypy traits in cannabis users.Schizophrenia research. Cognition · 2022Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
Abstract
The development of current neuroleptics was largely aiming to decrease excessive dopaminergic signaling in the striatum. However, the notion that abnormal dopamine creates psychotic symptoms by causing an aberrant assignment of salience that drives maladaptive learning chronically during disease development suggests a therapeutic value of early interventions that correct salience-related neural processing. The mesolimbic dopaminergic output is modulated by several interconnected brain-wide circuits centrally involving the hippocampus and key relays like the ventral and associative striatum, ventral pallidum, amygdala, bed nucleus of the stria terminalis, nucleus reuniens, lateral and medial septum, prefrontal and cingulate cortex, among others. Unraveling the causal relationships between these circuits using modern neuroscience techniques holds promise for identifying novel cellular-and ultimately molecular-treatment targets for reducing transition to psychosis and symptoms of schizophrenia. Imaging studies in humans have implicated a hyperactivity of the hippocampus as a robust and early endophenotype in schizophrenia. Experiments in rodents, in turn, suggested that the activity of its output region-the ventral subiculum-may modulate dopamine release from ventral tegmental area (VTA) neurons in the ventral striatum. Even though these observations suggested a novel circuit-level target for anti-psychotic action, no therapy has yet been developed along this rationale. Recently evaluated treatment strategies-at least in part-target excess glutamatergic activity, e.g. N-acetyl-cysteine (NAC), levetiracetam, and mGluR2/3 modulators. We here review the evidence for the central implication of the hippocampus-VTA axis in schizophrenia-related pathology, discuss its symptom-related implications with a particular focus on aberrant assignment of salience, and evaluate some of its short-comings and prospects for drug discovery.
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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.