Forebrain-Cerebellum Interactions in Trace Conditioning

描述（由申请人提供）：各种行为通常被称为“海马依赖”或“小脑依赖”。实际上，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。大量的前脑投射到小脑，突出了前脑和小脑之间相互作用的中心地位。在实践和概念上的优势，痕迹眼睑条件反射提供了一个机会，研究在一个明确定义的学习行为背景下的前脑-小脑相互作用。延迟眼睑调节相对直接地作用于小脑，而不需要前脑结构。相比之下，小脑、海马体和内侧前额叶皮层（mPFC）的损伤破坏了眼睑的调节。一个突出的理论认为，小脑不能通过痕迹输入来学习，前脑结构在沉默的痕迹间隔期间激活小脑输入，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。这一理论的关键检验——记录从苔藓纤维输入到小脑的海马体和激活

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.