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

适应性行为需要不断地评估和选择外部和内部环境中具有激励意义的信息。例如，在野外生存的生物体依赖于识别与奖励和惩罚偶发事件以及内部状态相关的不断变化的时空信号的能力，从而决定何时、何地和吃什么。我们实验室过去的工作已经确定了边缘皮质纹状体系统的区域在调节空间和情境线索对动机行为的控制方面至关重要。目前的建议将继续我们的努力，以描绘大脑网络和电路机制，促进部署适当的行为反应的生物学相关的线索，信号的存在和缺乏奖励或威胁，以及扩展我们的调查对动机行为的时间控制。该计划将采用多学科方法，利用体内光遗传学、化学遗传学、纤维光度法和免疫组织化学方法，结合定制大鼠行为范式，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，这些参与者是由信号奖励、威胁、缺乏奖励和安全的离散线索和环境招募的，以及信号时间信息的线索。2)研究在第一个目标中发现的中枢区域和回路在线索和时间控制动机行为中的因果作用。3)研究线索控制对动机行为的影响。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控制动机行为的回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.