ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
Bidirectional Regulation of Cognitive and Anxiety-like Behaviors by Dentate Gyrus Mossy Cells in Male and Female Mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Translational reprogramming of dentate gyrus peptidergic circuitry gates antidepressant efficacy.Molecular psychiatry · 2026Article
- Nicotinamide Riboside (NR) Supplementation Exerts Neuroprotective Effects in db/db Mouse Model of Type 2 Diabetes.Journal of molecular neuroscience : MN · 2026Article
- Loss of PLA2G4E compromises synaptic structure and cognitive outcomes in mice.Life science alliance · 2025Article
- Increased excitability of dentate gyrus mossy cells occurs early in life in the Tg2576 model of Alzheimer's disease.Alzheimer's research & therapy · 2025Article
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- Towards an Understanding of the Dentate Gyrus Hilus.Hippocampus · 2025Review
- Glial-restricted precursors stimulate endogenous cytogenesis and effectively recover emotional deficits in a model of cytogenesis ablation.Molecular psychiatry · 2024Article
- Article
- Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.bioRxiv : the preprint server for biology · 2024Article
- Article
- Circuit-based intervention corrects excessive dentate gyrus output in the fragile X mouse model.eLife · 2024Article
- Dopamine D2 receptors in hilar mossy cells regulate excitatory transmission and hippocampal function.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Distinct ACC Neural Mechanisms Underlie Authentic and Transmitted Anxiety Induced by Maternal Separation in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Circuit-based intervention corrects excessive dentate gyrus output in the Fragile X mouse model.bioRxiv : the preprint server for biology · 2023Article
- Sex-specific modulation of the medial prefrontal cortex by glutamatergic median raphe neurons.Science advances · 2023Article
- Assessments of dentate gyrus function: discoveries and debates.Nature reviews. Neuroscience · 2023Review
- Double-Edged Mossy Cells in Temporal Lobe Epilepsy: Evil in the Early Stage Through a BDNF-Dependent Strengthening Dentate Gyrus Circuit.Neuroscience bulletin · 2023Article
- Coordinated neurostimulation promotes circuit rewiring and unlocks recovery after spinal cord injury.The Journal of experimental medicine · 2023Article
- Glucagon-like peptide-1 receptor differentially controls mossy cell activity across the dentate gyrus longitudinal axis.Hippocampus · 2022Article
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Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The dentate gyrus (DG) of the hippocampus is important for cognition and behavior. However, the circuits underlying these functions are unclear. DG mossy cells (MCs) are potentially important because of their excitatory synapses on the primary cell type, granule cells (GCs). However, MCs also activate GABAergic neurons, which inhibit GCs. We used viral delivery of designer receptors exclusively activated by designer drugs (DREADDs) in mice to implement a gain- and loss-of-function study of MCs in diverse behaviors. Using this approach, manipulations of MCs could bidirectionally regulate behavior. The results suggest that inhibiting MCs can reduce anxiety-like behavior and improve cognitive performance. However, not all cognitive or anxiety-related behaviors were influenced, suggesting specific roles of MCs in some, but not all, types of cognition and anxiety. Notably, several behaviors showed sex-specific effects, with females often showing more pronounced effects than the males. We also used the immediate early gene c-Fos to address whether DREADDs bidirectionally regulated MC or GC activity. We confirmed excitatory DREADDs increased MC c-Fos. However, there was no change in GC c-Fos, consistent with MC activation leading to GABAergic inhibition of GCs. In contrast, inhibitory DREADDs led to a large increase in GC c-Fos, consistent with a reduction in MC excitation of GABAergic neurons, and reduced inhibition of GCs. Together, these results suggest that MCs regulate anxiety and cognition in specific ways. We also raise the possibility that cognitive performance may be improved by reducing anxiety.
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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.