FMRI OF NEURAL CIRCUITS IN EYEBLINK CONDITIONING

描述（改编自申请人的摘要）：通过在学习明确定义的行为范例期间和之后并参考适当的控制条件，研究它们的活动与行为变化并行，可以获得对关联学习和记忆基础的神经回路的更好理解。将在清醒家兔中使用功能性磁共振成像（fMRI），同时检查与眨眼条件反射相关的条件反射特异性血流动力学变化。首先，将用fMRI检查三种不同刺激途径（光和触须/触摸条件刺激（CS）和角膜空气抽吸非条件刺激（US））的血流动力学激活。其次，在CS与向眼睛吹气（US）配对的每次试验期间和之后，将检查在简单延迟条件反射期间激活的丘脑皮质感觉、边缘/前脑和小脑回路内的活动。在每只家兔中进行假条件训练、条件训练和巩固训练后拍摄的一系列功能图像将允许在每只动物中比较学习期间和之后与对照条件相比的血流动力学反应。注意力将集中在几个区域假设参与CR反射弧基于神经心理学和生理学分析使用其他技术，以及对大脑的其余部分，以找到尚未确定的区域与学习。第三，将检查视皮层依赖性辨别反转眨眼条件反射过程中激活的回路。这个范例应该激活边缘系统的组成部分，并提供一个有趣的比较感觉系统的功能时，CS在一个模态被用作CS+或CS-。在这个范例中的活动区域将与在简单的延迟范例中的活动区域进行比较，以确定对于依赖性学习至关重要的活动的位置或幅度。这些实验将产生重要的信息，在整个感觉-边缘-小脑系统的联想学习期间和之后，血流动力学活动的变化的位置和顺序。它们还将为非侵入性功能技术提供基础，以评估潜在治疗剂在正常衰老和阿尔茨海默病等条件下学习和记忆过程中增强神经系统功能的有效性，以及增强我们进一步了解哺乳动物大脑中联想学习的神经生物学底物的能力。

DESCRIPTION (adapted from applicant's abstract): A better understanding of neural circuits underlying associative learning and memory may be obtained by studying their activity in parallel with changes in behavior during and after learning a well-defined behavioral paradigm and in reference to appropriate control conditions. Functional magnetic resonance imaging (fMRI) will be used in the conscious rabbit to simultaneously examine conditioning-specific hemodynamic changes related to eyeblink conditioning. First, the hemodynamic activation of three different stimulus pathways (light and vibrissae/touch conditioned stimulus (CS) and corneal air puff unconditioned stimulus (US)) will be examined with fMRI. Second, activity within the thalamocortical sensory, limbic/forebrain and cerebellar circuitry activated during simple delay conditioning will be examined during and after each trial on which a CS is paired with airpuffs to the eye (US). A sequence of functional images taken after sessions of pseudoconditioning, conditioning and consolidation in each rabbit will allow comparisons within each animal of hemodynamic responses during and after learning as compared to the control conditions. Attention will be focused on several regions hypothesized to be involved in the CR reflex arc based on neuropsychological and physiological analyses done using other techniques, as well as on the rest of the brain to find regions not yet identified with learning. Third, the circuit activated during hippocampally- dependent discrimination reversal eyeblink conditioning will be examined. This paradigm should activate the components of the limbic system and offer an interesting comparison between sensory system function when a CS in a modality is used as a CS+ or CS-. The active regions in this paradigm will be compared with the regions active during the simpler delay paradigm to determine the locations or magnitude of activity that is critical for hippocampally-dependent learning. These experiments will yield significant information regarding the location and sequence of changes in hemodynamic activity during and after associative learning throughout the sensory-limbic-cerebellar system. They will also provide the basis for a noninvasive functional technique to evaluate the effectiveness of potential therapeutic agents for enhancing neural system function during learning and memory in conditions such as normal aging and Alzheimer's Disease as well as enhance our ability to further understand the neurobiological substrates of associative learning in mammalian brain.