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Choosing memory retrieval strategies: A critical role for inhibition in the dentate gyrus
Remembering the location of food is essential for survival. Rodents and humans employ mainly hippocampus-dependent spatial strategies, but when being stressed they shift to striatum-mediated stimulus-based strategies. To investigate underlying brain circuits, we tested mice with a heightened stress...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357949/ https://www.ncbi.nlm.nih.gov/pubmed/35958670 http://dx.doi.org/10.1016/j.ynstr.2022.100474 |
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author | Albrecht, Anne Müller, Iris Weiglein, Aliće Pollali, Evangelia Çalışkan, Gürsel Stork, Oliver |
author_facet | Albrecht, Anne Müller, Iris Weiglein, Aliće Pollali, Evangelia Çalışkan, Gürsel Stork, Oliver |
author_sort | Albrecht, Anne |
collection | PubMed |
description | Remembering the location of food is essential for survival. Rodents and humans employ mainly hippocampus-dependent spatial strategies, but when being stressed they shift to striatum-mediated stimulus-based strategies. To investigate underlying brain circuits, we tested mice with a heightened stress susceptibility due to a lack of the GABA-synthetizing enzyme GAD65 (GAD65−/− mice) in a dual solution task. Here, GAD65−/− mice preferred to locate a food reward in an open field via a proximal cue, while their wildtype littermates preferred a spatial strategy. The analysis of cFos co-activation across brain regions and of stress-induced mRNA expression changes of GAD65 pointed towards the hippocampal dorsal dentate gyrus (dDG) as a central structure for mediating stress effects on strategy choices via GAD65. Reducing the GAD65 expression locally in the dDG by a shRNA mediated knock down was sufficient to replicate the phenotype of the global GAD65 knock out and to increase dDG excitability. Using DREADD vectors to specifically interfere with dDG circuit activity during dual solution retrieval but not learning confirmed that the dDG modulates strategy choices and that a balanced excitability of this structure is necessary to establish spatial strategy preference. These data highlight the dDG as a critical hub for choosing between spatial and non-spatial foraging strategies. |
format | Online Article Text |
id | pubmed-9357949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-93579492022-08-10 Choosing memory retrieval strategies: A critical role for inhibition in the dentate gyrus Albrecht, Anne Müller, Iris Weiglein, Aliće Pollali, Evangelia Çalışkan, Gürsel Stork, Oliver Neurobiol Stress Original Research Article Remembering the location of food is essential for survival. Rodents and humans employ mainly hippocampus-dependent spatial strategies, but when being stressed they shift to striatum-mediated stimulus-based strategies. To investigate underlying brain circuits, we tested mice with a heightened stress susceptibility due to a lack of the GABA-synthetizing enzyme GAD65 (GAD65−/− mice) in a dual solution task. Here, GAD65−/− mice preferred to locate a food reward in an open field via a proximal cue, while their wildtype littermates preferred a spatial strategy. The analysis of cFos co-activation across brain regions and of stress-induced mRNA expression changes of GAD65 pointed towards the hippocampal dorsal dentate gyrus (dDG) as a central structure for mediating stress effects on strategy choices via GAD65. Reducing the GAD65 expression locally in the dDG by a shRNA mediated knock down was sufficient to replicate the phenotype of the global GAD65 knock out and to increase dDG excitability. Using DREADD vectors to specifically interfere with dDG circuit activity during dual solution retrieval but not learning confirmed that the dDG modulates strategy choices and that a balanced excitability of this structure is necessary to establish spatial strategy preference. These data highlight the dDG as a critical hub for choosing between spatial and non-spatial foraging strategies. Elsevier 2022-07-31 /pmc/articles/PMC9357949/ /pubmed/35958670 http://dx.doi.org/10.1016/j.ynstr.2022.100474 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Article Albrecht, Anne Müller, Iris Weiglein, Aliće Pollali, Evangelia Çalışkan, Gürsel Stork, Oliver Choosing memory retrieval strategies: A critical role for inhibition in the dentate gyrus |
title | Choosing memory retrieval strategies: A critical role for inhibition in the dentate gyrus |
title_full | Choosing memory retrieval strategies: A critical role for inhibition in the dentate gyrus |
title_fullStr | Choosing memory retrieval strategies: A critical role for inhibition in the dentate gyrus |
title_full_unstemmed | Choosing memory retrieval strategies: A critical role for inhibition in the dentate gyrus |
title_short | Choosing memory retrieval strategies: A critical role for inhibition in the dentate gyrus |
title_sort | choosing memory retrieval strategies: a critical role for inhibition in the dentate gyrus |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357949/ https://www.ncbi.nlm.nih.gov/pubmed/35958670 http://dx.doi.org/10.1016/j.ynstr.2022.100474 |
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