ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2017
Bidirectional Control of Anxiety-Related Behaviors in Mice: Role of Inputs Arising from the Ventral Hippocampus to the Lateral Septum and Medial Prefrontal Cortex.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed.
- The ventral hippocampus: computations, circuits and functions.Nature reviews. Neuroscience · 2026Review
- Rescuing anxiety by targeting the neuronal-astrocytic iron signaling axis in male mice.Signal transduction and targeted therapy · 2026Article
- The Role of Kappa-Opioid Receptor/Dynorphin System in Modulating Neural-Circuits of Depression and Anxiety-A Review.Journal of cellular and molecular medicine · 2026Review
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- Tetrodotoxin-resistant NaMolecular psychiatry · 2026Article
- Dorsal CA1 projections to nucleus accumbens and lateral septum differentially regulate social and locomotor behavior.Cerebral cortex (New York, N.Y. : 1991) · 2026Article
- Targeting the 5-HTCell & bioscience · 2026Article
- Dpp6 knockout mice exhibit increased ethanol conditioned place preference and acute ethanol-induced anxiolytic behavior.Alcohol, clinical & experimental research · 2026Article
- vCA1 SST neurons represent avoidance states that guide anxiety-related behavioral choices.bioRxiv : the preprint server for biology · 2026Article
- State and trait serotonin variations interact to shape the intrinsic connectivity and gradient architecture of the brain - a combined TPH2 genetics and tryptophan depletion study in men.Psychopharmacology · 2026Article
- Early life stress alters microglia in ventral hippocampus and dorsal CA2 associated with anxiety-like behavior in adolescent male rats.Experimental brain research · 2025Article
- An integrative model of perseverative thinking.Dialogues in clinical neuroscience · 2025Review
- Dopamine receptor 1-expressing cells in the ventral hippocampus encode cocaine-context associations.Research square · 2025Article
- Anxiety and Beyond: Diversity in Ventral Hippocampus Circuits and Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
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- Distinct subpopulations of parvalbumin neurons participating in divergent prefrontal functions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice.Cell & bioscience · 2025Article
- Models of human hippocampal specialization: a look at the electrophysiological evidence.Trends in cognitive sciences · 2025Review
- Hippocampal area CA2 activity supports social investigation following an acute social stress.Molecular psychiatry · 2025Article
70 more citing papers are in PubMed but not listed here.
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8 authors.
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Abstract
Anxiety is an adaptive response to potentially threatening situations. Exaggerated and uncontrolled anxiety responses become maladaptive and lead to anxiety disorders. Anxiety is shaped by a network of forebrain structures, including the hippocampus, septum, and prefrontal cortex. In particular, neural inputs arising from the ventral hippocampus (vHPC) to the lateral septum (LS) and medial prefrontal cortex (mPFC) are thought to serve as principal components of the anxiety circuit. However, the role of vHPC-to-LS and vHPC-to-mPFC signals in anxiety is unclear, as no study has directly compared their behavioral contribution at circuit level. We targeted LS-projecting vHPC cells and mPFC-projecting vHPC cells by injecting the retrogradely propagating canine adenovirus encoding Cre recombinase into the LS or mPFC, and injecting a Cre-responsive AAV (AAV8-hSyn-FLEX-hM3D or hM4D) into the vHPC. Consequences of manipulating these neurons were examined in well-established tests of anxiety. Chemogenetic manipulation of LS-projecting vHPC cells led to bidirectional changes in anxiety: activation of LS-projecting vHPC cells decreased anxiety whereas inhibition of these cells produced opposite anxiety-promoting effects. The observed anxiety-reducing function of LS-projecting cells was in contrast with the function of mPFC-projecting cells, which promoted anxiety. In addition, double retrograde tracing demonstrated that LS- and mPFC-projecting cells represent two largely anatomically distinct cell groups. Altogether, our findings suggest that the vHPC houses discrete populations of cells that either promote or suppress anxiety through differences in their projection targets. Disruption of the intricate balance in the activity of these two neuron populations may drive inappropriate behavioral responses seen in anxiety disorders.
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