Forebrain-Cerebellum Interactions in Trace Conditioning

描述（由申请人提供）：各种行为通常被称为“海马依赖性”或“小脑依赖性”。“事实上，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。 前脑向小脑的丰富投射突出了前脑和小脑之间相互作用的中心地位。 跟踪眼睑条件反射的实际和概念上的优势代表了一个机会，研究前脑小脑的相互作用的背景下，一个明确的学习行为。 延迟眼睑调节相对直接地参与小脑，并且不需要前脑结构。 相比之下，跟踪眼睑调节被破坏小脑，海马和内侧前额叶皮层（mPFC）的病变。 一个著名的理论认为，小脑不能学习与跟踪输入，前脑结构激活小脑的输入在沉默的跟踪间隔，这些输入参与正常的小脑学习机制，以获得适当的跟踪反应。 这一理论的关键检验--记录海马激活的从苔藓纤维到小脑的输入， 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的发现，即1）用苔藓纤维刺激证实小脑不能用痕迹输入学习，2）确定了痕迹条件反射所必需的苔藓纤维。 实验将完成作为前奏，在体内记录从苔藓纤维必不可少的痕迹条件和苔藓纤维直接激活的音调条件刺激。 这些细胞的听觉反应和学习依赖的活动，发展与跟踪条件反射的特点。 海马或mPFC的可逆失活可以用来识别驱动学习依赖性反应的输入的基本来源。 最后，使用苔藓纤维的刺激，这些学习依赖的反应，以支持小脑学习适当的跟踪响应的充分性将被测试。

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.