STRIATAL CIRCUITRY AND BEHAVIORAL FLEXIBILITY

人类以及其他物种的繁荣昌盛和生存从根本上取决于迅速适应不断变化的环境突发事件的能力。长期目标是了解大脑回路，该回路有助于在不断变化的条件下学习新规则。亨廷顿病和帕金森病的特点是纹状体细胞的改变，这些疾病的患者表现出认知灵活性的缺陷。这些发现表明，纹状体是一个可能在认知灵活性中发挥核心作用的大脑区域。然而，纹状体由不同的亚区组成，可能具有不同的认知和行为功能。了解特定的纹状体亚区是否有助于学习和灵活使用行为指导规则，例如快速策略，将为学习和行为灵活性的神经生物学提供重要的洞察力。最终，关于潜在行为灵活性的神经回路的信息可能会使开发有效的治疗方法来缓解亨廷顿病和帕金森病患者的认知症状。本研究旨在研究大鼠背内侧纹状体是否与不同形式的行为灵活性有关。在一组相关的实验中，评估了背内侧纹状体失活对视觉线索和转弯辨别规则的学习和颠倒的影响。具体到行为灵活性，这些实验将检查当大鼠必须在一个维度内移动(维度内移动)时，背内侧纹状体失活是否会损害学习，例如，从左转规则到右转规则，或者在维度之间(额外维度移动)，例如从视觉提示规则到转向规则。总体而言，拟议中的研究结果可以增加目前关于学习和行为灵活性背后的大脑回路的知识。

The thriving and survival of humans, as well as other species fundamentally depends on the ability to rapidly adapt to changing environmental contingencies. The long-term objective is to understand the brain circuitry that facilitates the learning of new rules with exposure to changing conditions. Huntington's and Parkinson's disease are marked by cellular alterations in the striatum and patients with these diseases exhibit deficits in cognitive flexibility. These findings suggest that the striatum is one brain area that may play a central role in cognitive flexibility. However, the striatum is made up of different subregions possibly subserving different cognitive and behavioral functions. Understanding whether particular striatal subregions facilitate the learning and flexible use of behavior-guiding rules, e.g. switiching strategies, will lend important insight into the neurobiology of learning and behavior flexibility. Ultimately, information obtained on the neurocircuitry underlying behavioral flexibility may enable the development of effective treatments for alleviating the cognitive symptomology observed in patients with Huntington's and Parkinson's disease. The present proposal examines whether the dorsomedial striatum in rats is involved in different forms of behavioral flexibility. In a related group of experiments, the effect of dorsomedial striatal inactivation on the learning and reversal of visual cue and turn discrimination rules are evaluated. Specific to behavioral flexibility, these experiments will examine whether dorsomedial striatal inactivation impairs learning when rats have to shift within a dimension (intra-dimensional shift), e.g. shift from a left turn rule to a right turn rule, or between a dimension (extra-dimension shift), e.g. shift from a visual cue rule to a turn rule. Overall, the findings from the proposed studies can increase the present knowledge about the brain circuitry underlying learning and behavioral flexibility.