Forebrain-Cerebellar Interactions During Learning

学习过程中前脑-小脑的相互作用

基本信息

批准号：
6613752
负责人：
JOHN F DISTERHOFT
金额：
$ 26.95万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-05-01 至 2007-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The cerebellum and its associated brainstem circuitry are required for learning and retaining simple conditioned reflexes of striated muscles, and the hippocampus is required to acquire and temporarily store stimulus associations for more complicated conditioning paradigms, such as trace conditioning. The overall goals of this proposal are to continue to characterize the neural substrates of these intermediate events in the hippocampus and other forebrain regions and, additionally, to begin to localize the brain regions underlying permanent storage of memory using hippocampally-dependent trace eyeblink conditioning in the rabbit. Our analysis of this circuit should lead to a more thorough understanding of the interrelationships among the cerebellum, hippocampus, and hippocampally-related forebrain structures, including the caudomedial prefrontal cortex (cmPFC), cortical association areas and the basal ganglia. Our aims will test a common hypothesis that the "memory trace" is transferred from the hippocampus to the cortex during acquisition and consolidation of learned responses. Our recent single neuron recordings indicate that the hippocampus and caudomedial prefrontal cortex mediate only a temporary role in learning the hippocampus-dependent trace eyeblink conditioned response. We propose that an increased excitability of association cortex neurons provides a necessary facilitation of pontine / mossy fiber inputs to the cerebellum, and that the basal ganglia provide necessary feedback from the cerebellum to the forebrain required to establish the neocortical changes. Single neuron activity will be recorded from large numbers of cells in rabbits during learning with multiple, independently moveable tetrodes to characterize activity at several key sites on the developing conditioned reflex arc. Inactivation will be done with reversible lesions, combined with single neuron recording and behavioral measurements, to evaluate the role of some regions. Our experimental program will begin testing the hypothesis that memories are stored in neocortical regions in a process dependent upon the engagement of the hippocampus and basal ganglia earlier in the learning process. Our data will have considerable relevance to better understanding the processes by which learning occurs in mammalian brain, including in human brain as we and others have shown important parallels in the processes by which humans and experimental animals acquire eyeblink conditioning. The results of these experiments will also be useful in the design of more appropriate treatments for learning deficits in young and aging individuals.

描述（由申请人提供）：小脑及其相关的脑干电路是学习和保留条纹肌肉的简单条件反射所需的，并且需要海马来获取并暂时存储刺激关联，以使其以更复杂的调理范式（例如痕量调节）。该提案的总体目标是继续表征海马和其他前脑区域中这些中间事件的神经底物，此外，还开始使用海马依赖性的痕量尊重兔子中的海马依赖的痕量尊重记忆的永久存储器的大脑区域。我们对该电路的分析应导致对小脑，海马和海马相关的前脑结构之间的相互关系，包括尾骨前额叶皮层（CMPFC），皮质结合区域和基础神经节。我们的目标将检验一个普遍的假设，即在获取和合并学习反应期间，“记忆痕迹”从海马转移到皮层。我们最近的单个神经元记录表明，海马和尾前额叶皮层仅介导在学习海马依赖性的微量扬声器条件响应中的临时作用。我们建议，缔合性皮质神经元的兴奋性增加为小脑的蓬托 /苔藓纤维输入提供了必要的促进，并且基底神经节提供了从小脑到建立新皮质变化所需的前脑的必要反馈。在学习过程中，将从兔子中的大量细胞中记录单个神经元活性，并以多个独立移动的四极管来表征发展条件反射弧的几个关键位点的活动。灭活将通过可逆病变与单个神经元记录和行为测量相结合，以评估某些区域的作用。我们的实验计划将开始检验以下假设：记忆在新皮层区域中存储在依赖于海马和基底神经节的过程中的过程中。我们的数据将具有相当大的相关性，以更好地了解哺乳动物大脑中学习的过程，包括在人脑中，因为我们和其他人在人类和实验动物获得眼睛闪烁的过程中显示出重要的相似之处。这些实验的结果也将在设计更合适的年轻人和老年人学习缺陷的治疗方法中很有用。