Striatum-projecting prefrontal cortex neurons support working memory maintenance
Maria Wilhelm1,2,3, Yaroslav Sych1,4, Aleksejs Fomins1,2
1Brain Research Institute, University of Zurich, 8057, Zurich, Switzerland.
Nature Communications
|November 3, 2023
Summary
Neurons projecting from the medial prefrontal cortex (mPFC) to the dorsomedial striatum (dmStr) are crucial for maintaining spatial working memory (WM). Their activity is specifically linked to the maintenance phase, not encoding or retrieval.
Area of Science:
- Neuroscience
- Cognitive Neuroscience
- Systems Neuroscience
Background:
- The medial prefrontal cortex (mPFC) plays a role in working memory (WM).
- The specific contribution of distinct mPFC projection pathways to WM remains largely unknown.
- Understanding these pathways is key to deciphering WM mechanisms.
Purpose of the Study:
- To investigate the role of dorsomedial striatum (dmStr)-projecting mPFC neurons in spatial working memory (WM).
- To determine if these neurons are involved in specific WM phases: encoding, maintenance, or retrieval.
Main Methods:
- Utilized optical recordings and optogenetic perturbations in male mice.
- Employed fiber photometry with GCaMP6m for neuronal activity monitoring.
- Conducted pharmacological interventions, including NMDA receptor blockade and HCN1 suppression.
Main Results:
- mPFC→dmStr neurons are essential for WM maintenance, but not encoding or retrieval in a T-maze task.
- Highest activity of mPFC→dmStr neurons was observed during the WM maintenance period.
- Inhibition during maintenance impaired performance, while enhancement alleviated WM deficits.
Conclusions:
- Dorsomedial striatum-projecting mPFC neurons critically support spatial working memory maintenance.
- A distinct subpopulation of these neurons is active during maintenance, separate from encoding/retrieval phases.
- Targeting the mPFC→dmStr pathway offers potential for understanding and modulating WM.
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