Neural mechanisms underlying behavioral flexibility

在随机环境中的适应行为对未来的成功和生存至关重要。在自然环境中，动物通常需要及时做出决定，评估结果以避免不希望看到的结果，并相应地更新它们的选择模式和行为，以促进灵活的反应。一系列研究表明，纹状体胆碱能间神经元的损伤(释放乙酰胆碱)和ACh的药物操作会损害行为的灵活性。尽管如此，当条件需要改变反应时，ACh在调节行为转换过程中的确切作用是缺乏的。重要的相关过程是调节和调节旧的、无效的信息的脱离，以及关于纹状体强化意外事件的新的、有效的信息的参与。到目前为止，我们已经成功地使用集成了双光子显微镜的虚拟现实系统设计了一个行为任务。利用这一点，我们还开始了纹状体ACh释放的同步成像，当小鼠参与规则切换的任务时。初步结果表明，ACh的动态时空模式是胆碱能中间神经元语境反应整合语境和奖赏以促进行为灵活性的一种可能方式。

Adaptive behaviours in stochastic environments are critical for future success and survival. In the natural environment, animals need to typically make decisions in a timely manner, assess outcomes to avoid undesirable ones, and update their choice patterns and behaviour accordingly, to promote flexible responding.A long line of studies showing that lesioning of striatal cholinergic interneurons (which release acetylcholine), and pharmacological manipulation of ACh release impaired behavioural flexibility. Notwithstanding, the precise role of ACh in mediating behavioural switching processes, when conditions demand a shift in response, is lacking. Of important relevance are the processes that regulate and mediate the disengagement of old, invalid information, and the engagement of new, valid information on reinforcement contingencies in the striatum. So far, we have successfully designed a behavioural task using a virtual reality system integrated with 2-photon microscope. Using this, we have also commenced simultaneous imaging of ACh release in striatum while mice are engaged in a task with rule switches. Preliminary results show that dynamic spatiotemporal patterning by ACh is a possible way for contextual responses of cholinergic interneurons to integrate context and reward to facilitate behavioral flexibility.