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Striatum-projecting prefrontal cortex neurons support working memory maintenance

Author

Listed:
  • Maria Wilhelm

    (University of Zurich
    University of Zurich and ETH Zurich
    ETH Zurich)

  • Yaroslav Sych

    (University of Zurich
    University of Strasbourg)

  • Aleksejs Fomins

    (University of Zurich
    University of Zurich and ETH Zurich)

  • José Luis Alatorre Warren

    (University of Zurich
    University of Oslo)

  • Christopher Lewis

    (University of Zurich)

  • Laia Serratosa Capdevila

    (University of Zurich)

  • Roman Boehringer

    (University of Zurich and ETH Zurich)

  • Elizabeth A. Amadei

    (University of Zurich and ETH Zurich)

  • Benjamin Grewe

    (University of Zurich and ETH Zurich
    University of Zurich and ETH Zurich
    University of Zurich)

  • Eoin C. O’Connor

    (Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd)

  • Benjamin J. Hall

    (Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd
    H. Lundbeck A/S)

  • Fritjof Helmchen

    (University of Zurich
    University of Zurich and ETH Zurich
    University of Zurich)

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.

Suggested Citation

  • 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 , 2023. "Striatum-projecting prefrontal cortex neurons support working memory maintenance," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42777-3
    DOI: 10.1038/s41467-023-42777-3
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    References listed on IDEAS

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