STRIATAL CIRCUITRY AND BEHAVIORAL FLEXIBILITY

人类以及其他物种的繁荣和生存从根本上取决于迅速适应变化的环境突发事件的能力。长期目标是了解在不断变化的条件下促进新规则学习的大脑回路。亨廷顿氏症和帕金森氏症的特征是纹状体的细胞改变，这些疾病的患者表现出认知灵活性的缺陷。这些发现表明，纹状体是大脑中可能在认知灵活性中发挥核心作用的一个区域。然而，纹状体由不同的亚区组成，可能服务于不同的认知和行为功能。了解特定纹状体亚区是否有助于学习和灵活使用行为指导规则，例如切换策略，将为学习和行为灵活性的神经生物学提供重要的见解。最终，获得的关于行为灵活性背后的神经回路的信息可能有助于开发有效的治疗方法，以减轻亨廷顿氏病和帕金森病患者观察到的认知症状。本研究探讨了大鼠的背内侧纹状体是否参与不同形式的行为灵活性。在一组相关的实验中，我们评估了背内侧纹状体失活对视觉线索和转身辨别规则的学习和逆转的影响。具体到行为灵活性，这些实验将检查背内侧纹状体失活是否会损害大鼠在一个维度内（内维度转移），例如从左转规则转移到右转规则，或在一个维度之间（外维度转移），例如从视觉提示规则转移到转弯规则。总的来说，拟议研究的发现可以增加目前对学习和行为灵活性背后的大脑回路的了解。

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.