RT Journal Article
SR Electronic
T1 Prefrontal top-down projections control context-dependent strategy selection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.12.14.472559
DO 10.1101/2021.12.14.472559
A1 Olivier Gschwend
A1 Tao Yang
A1 Daniëlle van de Lisdonk
A1 Xian Zhang
A1 Radhashree Sharma
A1 Bo Li
YR 2021
UL http://biorxiv.org/content/early/2021/12/15/2021.12.14.472559.abstract
AB 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 StatementThe authors have declared no competing interest.