Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Departments of Neurobiology and Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Cell Rep. 2022 Mar 1;38(9):110437. doi: 10.1016/j.celrep.2022.110437.
Cognitive flexibility enables effective switching between mental processes to generate appropriate responses. Cholinergic neurons (CNs) within the pedunculopontine nucleus (PPN) are associated with many functions, but their contribution to cognitive flexibility remains poorly understood. Here we measure PPN cholinergic activities using calcium indicators during the attentional set-shifting task. We find that PPN CNs exhibit increasing activities correlated with rewards during each stage and error trials in reversal stages, indicating sensitivity to rule switching. Inhibition of PPN cholinergic activity selectively impairs reversal learning, which improves with PPN CN activation. Activation of PPN CNs projecting to the substantia nigra pars compacta, mediodorsal thalamus, and parafascicular nucleus in a time-locked manner with reward improves reversal learning. Therefore, PPN CNs may encode not only reward signals but also the information of changing reward contingency that contributes to guiding reversal learning through output projections to multiple nuclei that participate in flexibility.
认知灵活性使人们能够在心理过程之间有效切换，从而产生适当的反应。被盖脑桥核（PPN）中的胆碱能神经元（CNs）与许多功能相关，但它们对认知灵活性的贡献仍知之甚少。在这里，我们在注意定势转移任务期间使用钙指示剂测量 PPN 胆碱能活动。我们发现，PPN CN 在每个阶段和反转阶段的错误试验中表现出与奖励相关的活动增加，表明它们对规则转换敏感。PPN 胆碱能活性的抑制选择性地损害反转学习，而 PPN CN 的激活可改善反转学习。与奖励同步激活投射到黑质致密部、中脑背侧丘脑和束旁核的 PPN CN 可改善反转学习。因此，PPN CN 不仅可能编码奖励信号，还可能编码改变奖励关联性的信息，通过投射到参与灵活性的多个核的输出来指导反转学习。
