Striatum-projecting prefrontal cortex neurons support working memory maintenance

Chernysheva, M.; Sych, Y.; Fomins, A.; Alatorre Warren, J. L.; Lewis, C. M.; Serratosa Capdevila, L.; Boehringer, R.; Amadei, E. A.; Grewe, B. F.; O'Connor, E. C.; Hall, B.; Helmchen, F.

doi:10.1101/2021.12.03.471159

bioRxiv · 10.1101/2021.12.03.471159

Striatum-projecting prefrontal cortex neurons support working memory maintenance

Chernysheva, M.·Sych, Y.·Fomins, A.·Alatorre Warren, J. L.·Lewis, C. M.·Serratosa Capdevila, L.·Boehringer, R.·Amadei, E. A.·Grewe, B. F.·O'Connor, E. C.·Hall, B.·Helmchen, F.

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Abstract

The medial prefrontal cortex (mPFC) and the dorsomedial striatum (dmStr) are linked to working memory (WM) but how striatum-projecting mPFC neurons contribute to WM encoding, maintenance, or retrieval remains unclear. Here, we probed mPFC[->]dmStr pathway function in freely-moving mice during a T-maze alternation test of spatial WM. Fiber photometry of GCaMP6m-labeled mPFC[->]dmStr projection neurons revealed strongest activity during the delay period that requires WM maintenance. Demonstrating causality, optogenetic inhibition of mPFC[->]dmStr neurons only during the delay period impaired performance. Conversely, enhancing mPFC[->]dmStr pathway activity--via pharmacological suppression of HCN1 or by optogenetic activation during the delay-- alleviated WM impairment induced by NMDA receptor blockade. Consistently, cellular-resolution miniscope imaging resolved preferred activation of >50% mPFC[->]dmStr neurons during WM maintenance. This subpopulation was distinct from neurons showing preference for encoding and retrieval. In all periods, including the delay, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance.

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Chernysheva, M., Sych, Y., Fomins, A., Alatorre Warren, J. L., Lewis, C. M., Serratosa Capdevila, L., Boehringer, R., Amadei, E. A., Grewe, B. F., O'Connor, E. C., Hall, B., Helmchen, F.. 2021-12-03. Striatum-projecting prefrontal cortex neurons support working memory maintenance. https://doi.org/10.1101/2021.12.03.471159

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