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Differential Control of Learning and Anxiety along the Dorsoventral Axis of the Dentate Gyrus
Open accessAbstract
The dentate gyrus (DG), in addition to its role in learning and memory, is increasingly implicated in the pathophysiology of anxiety disorders. Here, we show that, dependent on their position along the dorso-ventral axis of the hippocampus, DG granule cells (GCs) control specific features of anxiety and contextual learning. Using optogenetic techniques to either elevate or decrease GC activity, we demonstrate that GCs in the dorsal DG control exploratory drive and encoding, not retrieval, of contextual fear memories. In contrast, elevating the activity of GCs in the ventral DG has no effect on contextual learning but powerfully suppresses innate anxiety. These results suggest that strategies aimed at modulating the excitability of the ventral DG may be beneficial for the treatment of anxiety disorders.
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“The hippocampus itself appears to have a dorsal-ventral functional gradient, with the dorsal hippocampus encoding context more specifically, while the ventral hippocampus (vHPC) includes affective information as well [37].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [37]
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“The canonical role of the hippocampus in threat circuitry is to encode context-specific information of a threat trace, as it is crucial for an organism to be able to distinguish threats as belonging to a particular context.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [37]
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“Studies have shown that different parts of the hippocampus serve these different functions, with the dorsal hippocampus supporting spatial navigation learning and memory, and the ventral hippocampus as important for anxiety and stress regulation (Fanselow and Dong, 2010; Kheirbek et al., 2013).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Kheirbek et al., 2013
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“however, direct photostimulation of ventral dentate gyrus granule cells has been in fact found to suppress anxiety-like behaviors in the EPM and OFT91.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [91]
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Metadata
- Authors
- Kheirbek, M. A., Drew, L. J., Burghardt, N. S., Costantini, D. O., Tannenholz, L., Ahmari, S. E., Zeng, H., Fenton, A. A., & Hen, R.
- Affiliations
- New York State Psychiatric Institute (US)
- Allen Institute for Brain Science (US)
- SUNY Downstate Health Sciences University (US)
- Corresponding author
- Hen, René
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 77
- Issue
- 5
- Pages
- 955-968
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3595120
- OpenAlex
- W2069281265
- Semantic Scholar
- 3c538be529a4c5c54e7172e30f4e8504564c6a8d
- Cited by
- 713
- References
- 67
- Citations by year
- 2026: 29 · 2025: 62 · 2024: 46 · 2023: 39 · 2022: 63 · 2021: 59 · 2020: 67 · 2019: 74 · 2018: 65 · 2017: 50 · 2016: 46 · 2015: 43 · 2014: 51 · 2013: 19
- FWCI
- 28.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R37MH068542, K01MH099371, T32MH015174, K08MH087718)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- dentate gyrus, granule cells, dorsal-ventral axis, anxiety, contextual fear memory, contextual learning, memory encoding, memory retrieval, hippocampus, anxiety disorders, optogenetics
- MeSH terms
- Animals, Anxiety, Avoidance Learning, Behavior, Animal, Conditioning, Psychological, Fear, Immunohistochemistry, Learning, Male, Mental Recall, Stereotaxic Techniques, Dentate Gyrus, Mice, Optical Fibers, Opsins, Electrophysiological Phenomena, In Vitro Techniques
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