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，但不能以致命伤害或错过更容易捕获的机会为代价。大脑如何平衡忽视分心和保持行为灵活性这两个看似对立的过程？为什么这些过程会受到安非他明等改变多巴胺传递的药物的影响？这里提出的项目将在大鼠身上研究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影响前额叶皮质和腹侧纹状体的神经信号来影响这些过程，这两个脑区是参与目标定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，这是这些结构中与行为表现相关的神经信号的重要特征。其方法将是将实验和计算技术与长期目标相结合，即在决策中推进多巴胺功能的细胞-系统理论。来自表现良好的大鼠的神经记录将用于量化系统级神经动力学和多巴胺的影响，而来自脑片的记录将用于识别细胞水平的影响。非线性动力学领域的计算模型和分析工具将被用来在细胞和系统水平之间架起桥梁，并研究神经同步、多巴胺调制和行为之间的未被充分研究的关系。这一综合方法为新发现和生物、物理和计算科学之间的人员培训提供了许多机会。

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.