Striatum-projecting prefrontal cortex neurons support working memory maintenance
Abstract Neurons in the medial prefrontal cortex (mPFC) are functionally linked to working memory (WM) but how distinct projection pathways contribute to WM remains unclear. Based on optical recordings, optogenetic perturbations, and pharmacological interventions in male mice, we report here that do...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42777-3 |
| _version_ | 1797636808863907840 |
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| author | Maria Wilhelm Yaroslav Sych Aleksejs Fomins José Luis Alatorre Warren Christopher Lewis Laia Serratosa Capdevila Roman Boehringer Elizabeth A. Amadei Benjamin Grewe Eoin C. O’Connor Benjamin J. Hall Fritjof Helmchen |
| author_facet | Maria Wilhelm Yaroslav Sych Aleksejs Fomins José Luis Alatorre Warren Christopher Lewis Laia Serratosa Capdevila Roman Boehringer Elizabeth A. Amadei Benjamin Grewe Eoin C. O’Connor Benjamin J. Hall Fritjof Helmchen |
| author_sort | Maria Wilhelm |
| collection | DOAJ |
| description | Abstract Neurons in the medial prefrontal cortex (mPFC) are functionally linked to working memory (WM) but how distinct projection pathways contribute to WM remains unclear. Based on optical recordings, optogenetic perturbations, and pharmacological interventions in male mice, we report here that dorsomedial striatum (dmStr)-projecting mPFC neurons are essential for WM maintenance, but not encoding or retrieval, in a T-maze spatial memory task. Fiber photometry of GCaMP6m-labeled mPFC→dmStr neurons revealed strongest activity during the maintenance period, and optogenetic inhibition of these neurons impaired performance only when applied during this period. Conversely, enhancing mPFC→dmStr pathway activity—via pharmacological suppression of HCN1 or by optogenetic activation during the maintenance period—alleviated WM impairment induced by NMDA receptor blockade. Moreover, cellular-resolution miniscope imaging revealed that >50% of mPFC→dmStr neurons are active during WM maintenance and that this subpopulation is distinct from neurons active during encoding and retrieval. In all task periods, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance. |
| first_indexed | 2024-03-11T12:39:29Z |
| format | Article |
| id | doaj.art-3d1105829bda407eb32e041ea6573f18 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T12:39:29Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-3d1105829bda407eb32e041ea6573f182023-11-05T12:22:35ZengNature PortfolioNature Communications2041-17232023-11-0114111610.1038/s41467-023-42777-3Striatum-projecting prefrontal cortex neurons support working memory maintenanceMaria Wilhelm0Yaroslav Sych1Aleksejs Fomins2José Luis Alatorre Warren3Christopher Lewis4Laia Serratosa Capdevila5Roman Boehringer6Elizabeth A. Amadei7Benjamin Grewe8Eoin C. O’Connor9Benjamin J. Hall10Fritjof Helmchen11Brain Research Institute, University of ZurichBrain Research Institute, University of ZurichBrain Research Institute, University of ZurichBrain Research Institute, University of ZurichBrain Research Institute, University of ZurichBrain Research Institute, University of ZurichInstitute of Neuroinformatics, University of Zurich and ETH ZurichInstitute of Neuroinformatics, University of Zurich and ETH ZurichNeuroscience Center Zurich, University of Zurich and ETH ZurichNeuroscience & Rare Diseases, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche LtdNeuroscience & Rare Diseases, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche LtdBrain Research Institute, University of ZurichAbstract Neurons in the medial prefrontal cortex (mPFC) are functionally linked to working memory (WM) but how distinct projection pathways contribute to WM remains unclear. Based on optical recordings, optogenetic perturbations, and pharmacological interventions in male mice, we report here that dorsomedial striatum (dmStr)-projecting mPFC neurons are essential for WM maintenance, but not encoding or retrieval, in a T-maze spatial memory task. Fiber photometry of GCaMP6m-labeled mPFC→dmStr neurons revealed strongest activity during the maintenance period, and optogenetic inhibition of these neurons impaired performance only when applied during this period. Conversely, enhancing mPFC→dmStr pathway activity—via pharmacological suppression of HCN1 or by optogenetic activation during the maintenance period—alleviated WM impairment induced by NMDA receptor blockade. Moreover, cellular-resolution miniscope imaging revealed that >50% of mPFC→dmStr neurons are active during WM maintenance and that this subpopulation is distinct from neurons active during encoding and retrieval. In all task periods, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance.https://doi.org/10.1038/s41467-023-42777-3 |
| spellingShingle | Maria Wilhelm Yaroslav Sych Aleksejs Fomins José Luis Alatorre Warren Christopher Lewis Laia Serratosa Capdevila Roman Boehringer Elizabeth A. Amadei Benjamin Grewe Eoin C. O’Connor Benjamin J. Hall Fritjof Helmchen Striatum-projecting prefrontal cortex neurons support working memory maintenance Nature Communications |
| title | Striatum-projecting prefrontal cortex neurons support working memory maintenance |
| title_full | Striatum-projecting prefrontal cortex neurons support working memory maintenance |
| title_fullStr | Striatum-projecting prefrontal cortex neurons support working memory maintenance |
| title_full_unstemmed | Striatum-projecting prefrontal cortex neurons support working memory maintenance |
| title_short | Striatum-projecting prefrontal cortex neurons support working memory maintenance |
| title_sort | striatum projecting prefrontal cortex neurons support working memory maintenance |
| url | https://doi.org/10.1038/s41467-023-42777-3 |
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