Forebrain-Cerebellum Interactions in Trace Conditioning

微量调节中的前脑-小脑相互作用

• 批准号: 8392114
• 负责人: MICHAEL D MAUK
• 金额: $ 36.48万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-15 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8392114
• 关键词: Acetylcholine; Affect; Alzheimer' s Disease; Animals; Attention; Attention deficit hyperactivity disorder; Behavior; Behavioral; Cell Nucleus; Cells; Cerebellum; Data; Dementia; Disease; Extinction (Psychology); Eyelid structure; Goals; Health; Infusion procedures; Knowledge; Lateral; Learning; Lesion; Mechanics; Mediating; Memory impairment; Neurons; Oryctolagus cuniculus; Output; Pathway Analysis; Play; Pontine structure; Prefrontal Cortex; Prevention strategy; Primates; Property; Prosencephalon; Role; Savings; Senility; Short-Term Memory; Sorting - Cell Movement; Source; Specificity; Stimulus; System; Testing; Time; Training; Work; age related; basal forebrain; base; behavior influence; classical conditioning; conditioning; disorder prevention; eyelid conditioning; insight; learned behavior; nervous system disorder; neuromechanism; operation; response

DESCRIPTION (provided by applicant): We propose to use trace eyelid conditioning to study the neural mechanisms operating in prefrontal cortex to mediate working memory. We have demonstrated that trace eyelid conditioning in rabbit is a working memory task that involves the persistent activity of the so called "delay cells" of prefrontal cortex. There are many fundamental questions about delay cells and the mechanisms of working memory that have remained unanswered largely owing to limitations of studies in primates: the traditional system for working memory studies. Specifically, working with trace conditioning in rabbits makes it feasible to study the origins of delay cell activity in PFC: what roles are played by learning? what are the inputs to PFC that are necessary for delay cells? Because recordings are feasible in rabbits completely na¿ve to the task, which is not feasible with primates, such questions become feasible and affordable to answer. We will use recordings from PFC neurons to determine how delay cell activity arises and to characterize the rules that govern changes in delay cell responding as task demands are changed. Rabbit studies also make feasible analysis of the pathways projecting to prefrontal cortex that are involved in trace conditioning and delay cell activity. The completion of these studies will therefore yield fundamental new insights into the mechanisms responsible for the formation of working memories and their modulation by changes in environmental demands. Such knowledge will greatly facilitate our ability to develop strategies for the prevention or treatment of a host of neurological disorders that appear to relate to working memory deficits, including attention disorders and age-related dementias.

描述（由申请人提供）：我们建议使用微量眼睑调节来研究前额皮质中调节工作记忆的神经机制。我们已经证明，兔子的微量眼睑调节是一项工作记忆任务，涉及大脑的持续活动。关于延迟细胞和工作记忆机制的许多基本问题仍未得到解答，这很大程度上是由于灵长类动物研究的局限性：具体来说，工作记忆研究的传统系统。兔子的微量条件反射使得研究 PFC 中延迟细胞活动的起源成为可能：学习对 PFC 的输入起到什么作用，这些输入对于延迟细胞来说是完全可能的？完成这项对灵长类动物来说不可行的任务后，我们将使用 PFC 神经元的记录来确定延迟细胞活动如何产生，并描述控制延迟细胞响应任务要求的变化的规则。兔子研究还使得对投射到前额皮质的通路进行分析成为可能，这些通路涉及微量条件反射和延迟细胞活动，因此，这些研究的完成将为工作记忆的形成机制及其形成提供根本性的新见解。通过环境需求的变化进行调节。这些知识将极大地促进我们制定预防或治疗一系列似乎与工作记忆缺陷有关的神经系统疾病的策略，包括注意力障碍和与年龄相关的痴呆症。