Cortico-limbic-striatal network in stimulus and temporal control over adaptive behaviour

适应行为需要对外部和内部环境中具有激励意义的信息进行持续的评估和选择。例如，在野外生存的有机体依赖于它们识别与奖惩突发事件以及内部状态相关的不断变化的时空信号的能力，以便决定何时、何地和吃什么。我们实验室过去的研究发现，边缘皮质-纹状体系统的区域在调节对动机行为的空间和背景线索控制方面至关重要。目前的建议将继续努力描述大脑网络和回路机制，以促进对生物相关线索的适当行为反应的部署，这些线索表明存在或不存在奖励或威胁，并扩大我们对动机行为的时间控制的研究。拟议的计划将采用多学科方法，使用体内光遗传学、化学遗传学、纤维光度学和免疫组织化学方法，结合定制的大鼠行为范式，以实现以下目标：1)建立皮质-边缘-纹状体网络中的关键参与者，这些参与者由离散的线索和上下文招募，这些线索和上下文表示可获得奖励、威胁、缺乏奖励和免受威胁的安全，以及发出时间信息的线索。2)研究第一个目标中确定的中枢区域和回路在对动机行为的线索和时间控制中的因果作用。3)探讨动机行为线索控制中连接中枢区域之间的动态交互作用。这项研究将为大脑如何组织处理与奖励、安全和厌恶有关的时间和非时间信息，以及这些信息获得对动机行为的控制的电路机制提供关键和基本的见解。

Adaptive behaviour requires the continuous appraisal and selection of motivationally significant information in the external and internal environment. For instance, an organism surviving in the wild relies on their ability to discern changing spatiotemporal signals associated with reward and punishment contingencies as well as internal states in order to make decisions about when, where and what to eat. Past work from our laboratory has identified areas of the limbic cortico-striatal system to be critical in mediating spatial and contextual cue control over motivated behaviour. The present proposal will continue our endeavour to delineate the brain network and circuit mechanisms that facilitate the deployment of appropriate behavioural response to biologically relevant cues that signal the presence and absence of reward or threat, as well as extend our investigations into the temporal control over motivated behaviour. The proposed program will employ a multidisciplinary approach, using in vivo optogenetic, chemogenetic, fibre photometry and immunohistochemical methods in combination with customised rat behavioural paradigms, to achieve the following objectives: 1) To establish the key players in the cortico-limbic-striatal network that are recruited by discrete cues and context that signal the availability of reward, threat, absence of reward, and safety from threat, as well as cues signalling temporal information. 2) To investigate the causal role of the hub areas and circuits identified in the first objective, in cue and temporal control over motivated behaviour. 3) To investigate the dynamic interactions between connected hub areas in cue control over motivated behaviour. This research will provide critical and fundamental insights into how the brain is organized in processing temporal and non-temporal information pertaining to reward, safety and aversion and the circuit mechanisms by which such information gain control over motivated behaviour.