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”。 实际上，大脑功能在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。 小脑前脑投射的丰富性突出了前脑和小脑之间相互作用的中心突出。 痕量眼睑调节的实用和概念优势代表了在定义明确的学习行为的背景下研究前脑相互作用的机会。 延迟眼睑调节相对直接使小脑接触，并且不需要前脑结构。 相反，小脑，海马和内侧前额叶皮层（MPFC）的病变破坏了痕量眼睑调节。 一个突出的理论断言，小脑无法通过痕量输入来学习，前脑结构在沉默的痕量间隙期间激活小脑输入，并且这些输入会吸引正常的小脑学习机制以获得适当的痕量反应。 该理论的关键检验 - 记录从海马和海马激活的小脑的苔藓纤维输入 MPFC-不可能，因为这些苔藓纤维尚未鉴定。 拟议的研究扩展了具有苔藓纤维刺激确认的初步发现，即小脑无法通过痕量输入学习，并且2）鉴定出对痕量调节必不可少的苔藓纤维。 该实验将作为从痕量调节和直接由音调条件刺激直接激活的苔藓纤维中的苔藓纤维中记录体内记录的前奏。 这些细胞的听觉响应以及随着痕量调节而发展的学习依赖性活动将被表征。 然后，可以使用海马或MPFC的可逆失活来识别驱动与学习有关的响应的基本输入来源。 最后，使用刺激苔藓纤维，将测试这些依赖性响应以支持小脑学习适当的痕量反应的充分性。