FMRI OF NEURAL CIRCUITS IN EYEBLINK CONDITIONING

描述（改编自申请人的摘要）：在学习明确定义的行为范式期间和之后，并参考适当的控制条件，通过研究它们的活动与行为变化并行，可以更好地理解联想学习和记忆的神经回路。功能磁共振成像（fMRI）将用于有意识的兔子，同时检查与眨眼调节相关的调节特异性血流动力学变化。首先，用功能磁共振成像检查三种不同刺激途径（光和触须/触觉条件刺激（CS）和角膜充气非条件刺激（US））的血流动力学激活。其次，在简单延迟条件反射中激活的丘脑皮质感觉回路、边缘/前脑回路和小脑回路的活动将在每次试验期间和之后进行检查，其中CS与眼部充气相匹配（US）。在每只兔子的假条件作用、条件作用和巩固过程后拍摄的一系列功能图像，将使每只动物在学习期间和学习后的血流动力学反应与对照条件进行比较。注意将集中在几个区域，假设涉及到CR反射弧基于神经心理学和生理分析完成使用其他技术，以及在大脑的其余部分，以寻找尚未确定的区域与学习。第三，研究海马体依赖的辨别逆转眨眼条件反射过程中激活的回路。这种模式应该激活边缘系统的组成部分，并提供一个有趣的比较，当一个模态中的CS被用作CS+或CS-时，感觉系统的功能。这种模式下的活跃区域将与简单延迟模式下的活跃区域进行比较，以确定对海马体依赖性学习至关重要的活动的位置或程度。这些实验将提供关于在整个感觉-边缘-小脑系统的联想学习期间和之后血流动力学活动变化的位置和顺序的重要信息。它们还将为非侵入性功能技术提供基础，以评估在正常衰老和阿尔茨海默病等情况下增强学习和记忆过程中神经系统功能的潜在治疗药物的有效性，并增强我们进一步了解哺乳动物大脑联想学习的神经生物学基础的能力。

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.