Prefrontal transthalamic uncertainty processing drives flexible switching

• 成果类型: Article
• 署名作者: Lam, Norman H.; Mukherjee, Arghya; Wimmer, Ralf D.; Nassar, Matthew R.; Chen, Zhe Sage; Halassa, Michael M.
• 署名单位: Tufts University; Brown University; New York University; New York University; Tufts University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-1300
• DOI: 10.1038/s41586-024-08180-8
• 发表日期: 2025-01-02
• 关键词: tree shrew; cortex; REPRESENTATION; schizophrenia; connectivity; projections; decisions; inference; selection; thalamus

摘要

Making adaptive decisions in complex environments requires appropriately identifying sources of error1,2. The frontal cortex is critical for adaptive decisions, but its neurons show mixed selectivity to task features3 and their uncertainty estimates4, raising the question of how errors are attributed to their most likely causes. Here, by recording neural responses from tree shrews (Tupaia belangeri) performing a hierarchical decision task with rule reversals, we find that the mediodorsal thalamus independently represents cueing and rule uncertainty. This enables the relevant thalamic population to drive prefrontal reconfiguration following a reversal by appropriately attributing errors to an environmental change. Mechanistic dissection of behavioural switching revealed a transthalamic pathway for cingulate cortical error monitoring5,6 to reconfigure prefrontal executive control7. Overall, our work highlights a potential role for the thalamus in demixing cortical signals while providing a low-dimensional pathway for cortico-cortical communication. By examining neural responses from tree shrews performing hierarchical decision tasks with rule reversals, the authors identify a thalamocortical mechanism for regulating cognitive flexibility.