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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Kheirbek, Mazen A., Drew, Liam J., Burghardt, Nesha S., Costantini, Daniel O., Tannenholz, Lindsay, Ahmari, Susanne E., Zeng, Hongkui, Fenton, André A., Hen, René·2013·Neuron

DOI 10.1016/j.neuron.2012.12.038PMC PMC3595120

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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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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
ORCID: Kheirbek, Mazen A.
Burghardt, Nesha S.
Ahmari, Susanne E.
Zeng, Hongkui
Fenton, André A.
Hen, René
Venue: Neuron
Publisher: Elsevier BV
Published: 2013-03
Volume: 77
Issue: 5
Pages: 955-968
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2012.12.038
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
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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Differential Control of Learning and Anxiety along the Dorsoventral Axis of the Dentate Gyrus

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