Dopamine modulation of neural dynamics and behavioral flexibility

有效的目标实现通常需要忽略干扰的能力，同时保持对行为相关刺激的反应。例如，捕食者必须专注于猎物，但不能以致命的伤害或错过更容易捕获的机会为代价。大脑是如何平衡这两个看似相反的过程的：忽略分心和保持行为灵活性？为什么这些过程会受到改变多巴胺传递的药物的影响，比如安非他明？这里提出的项目将研究大鼠参与这些过程的神经机制，以更好地了解人类大脑如何完成这些功能。目的是了解多巴胺如何通过其对前额叶皮层和腹侧纹状体的神经信号的影响来影响这些过程，这是涉及目标导向行为的关键大脑区域。该项目的一个特别重点是评估多巴胺如何影响神经同步和振荡，这是与行为表现相关的这些结构中的神经信号的重要特征。该方法将实验和计算技术与推进多巴胺在决策中的细胞到系统功能理论的长期目标相结合。来自行为老鼠的神经记录将被用来量化系统级的神经动力学和多巴胺的影响，而来自大脑切片的记录将被用来确定细胞水平的影响。来自非线性动力学领域的计算模型和分析工具将用于在细胞和系统水平之间架起桥梁，并研究神经同步，多巴胺调节和行为之间尚未研究的关系。这种综合方法为新发现提供了许多机会，并为培养生物学、物理学和计算科学之间的人员提供了机会。

Efficient goal attainment often requires the ability to ignore distractions while remaining responsive to behaviorally relevant stimuli. For instance, a predator must focus on its prey, but not at the expense of mortal injury or the missed opportunity for an easier catch. How does the brain balance the seemingly opposing processes of ignoring distraction and maintaining behavioral flexibility, and why are these affected by drugs that alter dopamine transmission, such as amphetamines? The project proposed here will investigate neural mechanisms involved in these processes in rats to better understand how the human brain might accomplish such functions. The objective is to understand how dopamine affects these processes through its influence on neural signaling in the prefrontal cortex and ventral striatum, key brain regions involved in goal-directed behavior. A particular focus of the project is to assess how dopamine influences neural synchronization and oscillations, which are important features of neural signaling in these structures related to behavioral performance. The approach will be to integrate experimental and computational techniques with the long-term goal of advancing a cell-to-systems theory of dopamine function in decision-making. Neural recordings from behaving rats will be used to quantify systems-level neural dynamics and the effects of dopamine, while recordings from brain slices will be used to identify effects at the cellular level. Computational models and analytical tools from the field of nonlinear dynamics will be used to bridge between cellular and systems levels, and investigate the understudied relationship between neural synchronization, dopamine modulation and behavior. This integrated approach provides numerous opportunities for new discoveries and for training personnel at the interface between biology, physics and computational science.