Cited by 713Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

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Differential Control of Learning and Anxiety along the Dorsoventral Axis of the Dentate Gyrus

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Abstract

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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Crossref · 10.1016/j.neuron.2012.12.038

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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)
OpenAlex
W2069281265
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
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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