Cholinergic neurons in the pedunculopontine nucleus guide reversal learning by signaling the changing reward contingency
Cholinergic neurons in the pedunculopontine nucleus guide reversal learning by signaling the changing reward contingency
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DOI：
10.1016/j.celrep.2022.110437
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发表时间：
2022-03-01
期刊：
影响因子：
8.8
通讯作者：
Zhang, Bao-Rong
中科院分区：
文献类型：
--
作者：
Ruan, Yang;Li, Kai-Yuan;Zhang, Bao-Rong
认知灵活性能够在心理过程之间有效切换，从而产生适当的反应。桥脚核（PPN）内的胆碱能神经元（CNs）与许多功能有关，但它们对认知灵活性的贡献仍然知之甚少。在这里，我们测量PPN胆碱能活动使用钙指标在注意力转移任务。我们发现PPN神经网络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，表明对规则转换的敏感性。抑制PPN胆碱能活性选择性地损害逆转学习，这种情况随着PPN CN的激活而改善。以带奖励的时间锁定方式激活投射到黑质致密部、丘脑中背侧和束旁核的PPN神经网络可以改善逆转学习。因此，PPN神经网络不仅可以编码奖励信号，还可以编码奖励偶然性变化的信息，这些信息有助于通过输出投射到参与灵活性的多个核来指导反转学习。
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.