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  Dentate gyrus is needed for memory retrieval

Carretero-Guillén, A., Treviño, M., Gómez-Climent, M. Á., Dogbevia, G. K., Bertocchi, I., Sprengel, R., et al. (2024). Dentate gyrus is needed for memory retrieval. Molecular Psychiatry, 1-12. doi:10.1038/s41380-024-02546-0.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000F-4677-D Version Permalink: https://hdl.handle.net/21.11116/0000-000F-4BF0-E
Genre: Journal Article

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 Creators:
Carretero-Guillén, Alejandro, Author
Treviño, Mario1, Author           
Gómez-Climent, María Ángeles, Author
Dogbevia, Godwin K.1, Author           
Bertocchi, Ilaria1, Author           
Sprengel, Rolf1, Author           
Larkum, Matthew E., Author
Vlachos, Andreas, Author
Gruart, Agnès, Author
Delgado-García, José M., Author
Hasan, Mazahir T., Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

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 Abstract: The hippocampus is crucial for acquiring and retrieving episodic and contextual memories. In previous studies, the inactivation of dentate gyrus (DG) neurons by chemogenetic- and optogenetic-mediated hyperpolarization led to opposing conclusions about DG's role in memory retrieval. One study used Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-mediated clozapine N-oxide (CNO)-induced hyperpolarization and reported that the previously formed memory was erased, thus concluding that denate gyrus is needed for memory maintenance. The other study used optogenetic with halorhodopsin induced hyperpolarization and reported and dentate gyrus is needed for memory retrieval. We hypothesized that this apparent discrepancy could be due to the length of hyperpolarization in previous studies; minutes by optogenetics and several hours by DREADD/CNO. Since hyperpolarization interferes with anterograde and retrograde neuronal signaling, it is possible that the memory engram in the dentate gyrus and the entorhinal to hippocampus trisynaptic circuit was erased by long-term, but not with short-term hyperpolarization. We developed and applied an advanced chemogenetic technology to selectively silence synaptic output by blocking neurotransmitter release without hyperpolarizing DG neurons to explore this apparent discrepancy. We performed in vivo electrophysiology during trace eyeblink in a rabbit model of associative learning. Our work shows that the DG output is required for memory retrieval. Based on previous and recent findings, we propose that the actively functional anterograde and retrograde neuronal signaling is necessary to preserve synaptic memory engrams along the entorhinal cortex to the hippocampal trisynaptic circuit.

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Language(s): eng - English
 Dates: 2024-03-032023-03-072024-03-262024-04-12
 Publication Status: Published online
 Pages: 12
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: URI: https://pubmed.ncbi.nlm.nih.gov/38609585/
DOI: 10.1038/s41380-024-02546-0
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Title: Molecular Psychiatry
Source Genre: Journal
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Publ. Info: Houndmills, Hampshire, UK : Stockton Press
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: 1 - 12 Identifier: ISSN: 1359-4184
CoNE: https://pure.mpg.de/cone/journals/resource/954925619131