Neural mechanisms underlying behavioral flexibility

行为灵活性背后的神经机制

• 批准号: 22K15633
• 负责人: サポン ギデオン
• 金额: $ 2.83万
• 依托单位: Okinawa Institute of Science and Technology Graduate University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K15633/
• 关键词: Acetylcholine; flexibility; Reversal learning; dopamine; acetylcholine

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.

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策，评估结果以避免不期望的结果，并相应地更新其选择模式和行为，以促进灵活的反应。一系列研究表明，纹状体胆碱能中间神经元（释放乙酰胆碱）的损伤和ACh释放的药理学操作损害了行为灵活性。尽管如此，乙酰胆碱在介导行为转换过程中的确切作用，当条件要求改变反应，是缺乏的。重要的相关性是调节和介导旧的、无效信息的脱离以及新的、有效信息与纹状体中强化偶然事件的参与的过程。到目前为止，我们已经成功地设计了一个行为任务，使用虚拟现实系统集成了双光子显微镜。利用这一点，我们也开始同时成像乙酰胆碱释放纹状体，而小鼠从事的任务与规则开关。初步结果表明，动态时空图案的乙酰胆碱是一种可能的方式，为背景的胆碱能中间神经元的反应，整合背景和奖励，以促进行为的灵活性。