Elevated activity in the dorsal dentate gyrus reduces expression of fear memory after fear extinction training
Open accessAbstract
Background: Effectively reducing the expression of certain aversive memories (fear or trauma memories) with extinction training is generally viewed to be therapeutically important. A deeper understanding of the biological basis for a more effective extinction process is also of high scientific importance. Methods: Our study involved intraventricular injection or local injection into the dorsal dentate gyrus of anti-neuregulin 1 antibodies (anti-NRG1) before fear extinction training, followed by testing the expression of fear memory 24 hours afterward or 9 days later. We used local injection of chemogenetic or optogenetic viruses into the dorsal dentate gyrus to manipulate the activity of the dorsal dentate gyrus and test the expression of fear memory. We also examined the effect of deep brain stimulation in the dorsal dentate gyrus on the expression of fear memory. Results: Mice that received intraventricular injection with anti-NRG1 antibodies exhibited lower expression of fear memory and increased density of activated excitatory neurons in the dorsal dentate gyrus. Injection of anti-NRG1 antibodies directly into the dorsal dentate gyrus also led to lower expression of fear memory and more activated neurons in the dorsal dentate gyrus. Inhibiting the activity of dorsal dentate gyrus excitatory neurons using an inhibitory designer receptor exclusively activated by designer drugs (DREADD) eliminated the effects of the anti-NRG1 antibodies. Enhancing the activity of the dorsal dentate gyrus with an excitatory DREADD or optogenetic stimulation resulted in lower expression of fear memory in mice that did not receive infusion of anti-NRG1 antibodies. Deep brain stimulation in the dorsal dentate gyrus effectively suppressed expression of fear memory, both during and after fear extinction training. Limitations: The mechanism for the contribution of the dorsal dentate gyrus to the expression of fear memory needs further exploration. Conclusion: Activation of the dorsal dentate gyrus may play an important role in modulating the expression of fear memory; its potential use in fear memory extinction is worthy of further exploration.
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These ROIs have been previously associated with fear memory and align with work at the circuit level.
“These ROIs have been previously associated with fear memory56,59-66 and align with work at the circuit level62.”
From Magnetic resonance microscopy maps widespread effects of Alzheimer’s disease on brain structures and behavior in mice (2026) · cites this paper as [65]
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- Authors
- Zhang, Y., Wang, Z., Ju, J., Liao, J., & Zhou, Q.
- Affiliations
- Sun Yat-sen University (CN)
- Corresponding author
- Zhou, Qiang
- Venue
- Journal of Psychiatry and Neuroscience
- Publisher
- Canadian Science Publishing
- Published
- 2021-05
- Volume
- 46
- Issue
- 3
- Pages
- E390-E401
- ISSN
- 1180-4882 (ISSN-L)
- 1488-2434
- PMC
- PMC8327976
- OpenAlex
- W3165261103
- Cited by
- 14
- References
- 55
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 3 · 2022: 1
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Journal of Psychiatry and Neuroscience (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Shenzhen Bay Laboratory (SZBL2019062801003)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- dorsal dentate gyrus, fear memory, fear extinction, neuregulin-1, deep brain stimulation, DREADD, optogenetics, chemogenetics, memory expression
- MeSH terms
- Animals, Extinction, Psychological, Fear, Male, Memory, Neurons, Dentate Gyrus, Mice
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