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DREADD in Parvalbumin Interneurons of the Dentate Gyrus Modulates Anxiety, Social Interaction and Memory Extinction
Open accessAbstract
Parvalbumin (PV)-positive interneurons in the hippocampus play a critical role in animal memory, such as spatial working memory. However, how PV-positive interneurons in the subregions of the hippocampus affect animal behaviors remains poorly defined. Here, we achieved specific and reversible activation of PV-positive interneurons using designer receptors exclusively activated by designer drugs (DREADD) technology. Inducible DREADD expression was demonstrated in vitro in cultured neurons, in which co-transfection of the hM3D-Gq-mCherry vector with a Cre plasmid resulted in a cellular response to hM3Dq ligand clozapine-N-oxide (CNO) stimulation. In addition, the dentate gyrus (DG) of PV-Cre mice received bilateral injection of control lentivirus or lentivirus expressing double floxed hM3D-Gq-mCherry. Selective activation of PV-positive interneurons in the DG did not affect locomotor activity or depression-related behavior in mice. Interestingly, stimulation of PV-positive interneurons induced an anxiolytic effect. Activation of PVpositive interneurons appears to impair social interaction to novelty, but has no effect on social motivation. However, this defect is likely due to the anxiolytic effect as the exploratory behavior of mice expressing hM3DGq is significantly increased. Mice expressing hM3D-Gq did not affect novel object recognition. Activation of PV-positive interneurons in the DG maintains intact cued and contextual fear memory but facilitates fear extinction. Collectively, our results demonstrated that proper control of PV interneurons activity in the DG is critical for regulation of the anxiety, social interaction and fear extinction. These results improve our fundamental understanding of the physiological role of PV-positive interneurons in the hippocampus.
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“However, lesions in the dorsal dentate gyrus did not induce NOP/OPP deficits in rats (Beselia et al., 2010), and DREADD activation of GABAergic parvalbumin neurons in the dentate gyrus also showed no effect in the NOP test, but influenced anxiety-like behaviors, social novelty and contextual fear extinction in mice (Zou et al., 2016).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Zou et al., 2016
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Hippocampal GABAergic Inhibitory Interneurons
Pelkey, K. A., Chittajallu, R., Craig, M. T., Tricoire, L., Wester, J. C., & McBain, C. J. (2017) · Physiological Reviews · doi:10.1152/physrev.00007.2017 · Cited by 889
A viral strategy for targeting and manipulating interneurons across vertebrate species
Dimidschstein, J., Chen, Q., Tremblay, R., Rogers, S. L., Saldi, G.-A., Guo, L., Xu, Q., Liu, R., Lu, C., Chu, J., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4430 · Cited by 541
Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Interventions
Fogaça, M. V., & Duman, R. S. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00087 · Cited by 396
Chao, O. Y., de Souza Silva, M. A., Yang, Y.-M., & Huston, J. P. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.007 · Cited by 158
Anxiety and hippocampal neuronal activity: Relationship and potential mechanisms
Ghasemi, M., Navidhamidi, M., Rezaei, F., Azizikia, A., & Mehranfard, N. (2021) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-021-00973-y · Cited by 175
Metadata
- Authors
- Zou, D., Chen, L., Deng, D., Jiang, D., Dong, F., McSweeney, C., Zhou, Y., Liu, L., Chen, G., Wu, Y., & Mao, Y.
- Affiliations
- Pennsylvania State University (US)
- Guangxi Medical University (CN)
- Corresponding author
- Wu, Y.
- Mao, Y.
- Venue
- Current Molecular Medicine
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2016-01-08
- Volume
- 16
- Issue
- 1
- Pages
- 91-102
- ISSN
- 1566-5240 (ISSN-L)
- PMC
- PMC4997952
- OpenAlex
- W2202096406
- Cited by
- 112
- References
- 64
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 3 · 2023: 8 · 2022: 22 · 2021: 23 · 2020: 14 · 2019: 14 · 2018: 3 · 2017: 9 · 2016: 4
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Current Molecular Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Natural Science Foundation of China (81160167, 81360201)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- parvalbumin interneurons, dentate gyrus, DREADD, clozapine-N-oxide, optogenetic stimulation, anxiety, social interaction, fear extinction, fear memory, hippocampus, social motivation, novel object recognition
- MeSH terms
- Animals, Anxiety, Anxiety Disorders, Depression, Fear, Hippocampus, Humans, Interneurons, Interpersonal Relations, Male, Memory, Motor Activity, Parvalbumins, Dentate Gyrus, Mice, HEK293 Cells
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