Forebrain-Cerebellum Interactions in Trace Conditioning

微量调节中的前脑-小脑相互作用

• 批准号: 7497551
• 负责人: MICHAEL D MAUK
• 金额: $ 28.08万
• 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 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497551
• 关键词: Animals; Auditory; Behavior; Behavioral; Brain; Cell Nucleus; Cells; Cerebellum; Condition; Conditioned Stimulus; Data; Dorsal; Eyelid structure; Failure; Hippocampus (Brain); Individual; Infusion procedures; Lateral; Learning; Lesion; Medial; Mediating; Methods; Muscimol; Output; Pattern; Phase; Pontine structure; Prefrontal Cortex; Principal Investigator; Property; Prosencephalon; Relative (related person); Research; Series; Source; Structure; System; Testing; Time; Training; Work; auditory stimulus; base; classical conditioning; conditioning; density; eyelid conditioning; in vivo; mossy fiber; neural circuit; programs; relating to nervous system; research study; response; theories

DESCRIPTION (provided by applicant): Various behaviors are often referred to as "hippocampal dependent" or "cerebellar dependent." In reality, brain function largely involves interactions between brain systems, although these interactions are difficult to study. The abundance of forebrain projections to cerebellum highlights the central prominence of interactions between forebrain and cerebellum. The practical and conceptual advantages of trace eyelid conditioning represent an opportunity to study forebrain-cerebellum interactions in the context of a well-defined learned behavior. Delay eyelid conditioning engages the cerebellum relatively directly and does not require forebrain structures. In contrast, trace eyelid conditioning is disrupted by lesions of the cerebellum, hippocampus and medial prefrontal cortex (mPFC). A prominent theory asserts that cerebellum cannot learn with trace inputs, that forebrain structures activate cerebellar inputs during the silent trace-interval, and that these inputs engage normal cerebellar learning mechanisms to acquire appropriate trace responses. The key test of this theory - to record from the mossy fiber inputs to cerebellum activated by hippocampus and mPFC - has not been possible because these mossy fibers had not been identified. The proposed studies extend preliminary findings that have 1) confirmed with mossy fiber stimulation that cerebellum cannot learn with trace inputs, and 2) identified the mossy fibers essential for trace conditioning. The experiments will be completed as a prelude to recording in vivo from the mossy fibers essential for trace conditioning and from the mossy fibers activated directly by the tone conditioned stimulus. The auditory responses of these cells and the learning-dependent activity that develops with trace conditioning will be characterized. Reversible inactivation of hippocampus or mPFC can then be used to identify essential sources of input that drive the learning-dependent responses. Finally, using stimulation of mossy fibers, the sufficiency of these learning dependent responses to support cerebellar learning of appropriate trace responses will be tested.

描述（由申请人提供）：各种行为通常被称为“海马依赖性”或“小脑依赖性”。 事实上，大脑功能很大程度上涉及大脑系统之间的相互作用，尽管这些相互作用很难研究。 前脑向小脑的大量投射凸显了前脑和小脑之间相互作用的中心地位。 微量眼睑调节的实践和概念优势代表了在明确的学习行为背景下研究前脑-小脑相互作用的机会。 延迟眼睑调节相对直接地涉及小脑，并且不需要前脑结构。 相比之下，小脑、海马体和内侧前额皮质（mPFC）的损伤会破坏眼睑的微量调节。 一个著名的理论认为，小脑无法通过痕迹输入进行学习，前脑结构在无声痕迹间隔期间激活小脑输入，并且这些输入参与正常的小脑学习机制以获得适当的痕迹反应。 该理论的关键测试 - 记录从海马体激活的苔藓纤维输入到小脑的过程 mPFC - 不可能，因为这些苔藓纤维尚未被识别。 拟议的研究扩展了初步发现，1）通过苔藓纤维刺激证实小脑无法通过微量输入进行学习，2）确定了微量调节所必需的苔藓纤维。 这些实验将作为在体内记录微量调节所必需的苔藓纤维和直接由音调调节刺激激活的苔藓纤维的前奏而完成。 这些细胞的听觉反应以及通过微量调节而发展的学习依赖性活动将被表征。 海马体或 mPFC 的可逆失活可用于识别驱动学习依赖性反应的重要输入源。 最后，通过刺激苔藓纤维，将测试这些学习依赖性反应是否足以支持小脑学习适当的痕迹反应。