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Prefrontal top-down projections control context-dependent strategy selection

Olivier Gschwend, Tao Yang, Daniëlle van de Lisdonk, Xian Zhang, Radhashree Sharma, View ORCID ProfileBo Li
doi: https://doi.org/10.1101/2021.12.14.472559
Olivier Gschwend
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
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  • For correspondence: gschwen@cshl.edu bli@cshl.edu
Tao Yang
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
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Daniëlle van de Lisdonk
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
2Center for Neuroscience, University of Amsterdam, Amsterdam, the Netherlands
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Xian Zhang
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
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Radhashree Sharma
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
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Bo Li
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
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  • ORCID record for Bo Li
  • For correspondence: gschwen@cshl.edu bli@cshl.edu
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Abstract

The rules governing behavior often vary with behavioral contexts. As a consequence, an action rewarded in one context may be discouraged in another. Animals and humans are capable of switching between behavioral strategies under different contexts and acting adaptively according to the variable rules, a flexibility that is thought to be mediated by the prefrontal cortex (PFC)1–4. However, how the PFC orchestrates context-dependent switch of strategies remains unclear. Here we show that pathway-specific projection neurons in the medial PFC (mPFC) differentially contribute to context-instructed strategy selection. In a decision-making task in which mice have been trained to flexibly switch between a previously established rule and a newly learned rule in a context-dependent manner, the activity of mPFC neurons projecting to the dorsomedial striatum encodes the contexts, and further represents decision strategies conforming to the old and new rules. Moreover, the activity of these neuron is required for context-instructed strategy selection. In contrast, the activity of mPFC neurons projecting to the ventral midline thalamus does not discriminate between the contexts, and represents the old rule even if mice have adopted the new one; furthermore, these neurons act to prevent the strategy switch under the new rule. Our results suggest that the mPFC→striatum pathway promotes flexible strategy selection guided by contexts, whereas the mPFC→thalamus pathway favors fixed strategy selection by preserving old rules. Balanced activity between the two pathways may be critical for adaptive behaviors.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 15, 2021.
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Prefrontal top-down projections control context-dependent strategy selection
Olivier Gschwend, Tao Yang, Daniëlle van de Lisdonk, Xian Zhang, Radhashree Sharma, Bo Li
bioRxiv 2021.12.14.472559; doi: https://doi.org/10.1101/2021.12.14.472559
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Prefrontal top-down projections control context-dependent strategy selection
Olivier Gschwend, Tao Yang, Daniëlle van de Lisdonk, Xian Zhang, Radhashree Sharma, Bo Li
bioRxiv 2021.12.14.472559; doi: https://doi.org/10.1101/2021.12.14.472559

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