Cortical Acetylcholine Release and Associative Learning (pilot)

皮质乙酰胆碱释放和联想学习（试点）

• 批准号: 7312219
• 负责人: Allen E Butt
• 金额: $ 4.98万
• 依托单位: CALIFORNIA STATE UNIV SAN BERNARDINO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7312219
• 关键词: acetylcholine; association learning; attention; behavioral /social science research tag; conditioning; laboratory rat; minority institution research support; neurotransmitter transport; sensory cortex; stimulus /response

The proposed experiments involve the use of in vivo microdialysis and high-performance liquid chromotography/electrochemical detection techniques to measure the amount of the neurotransmitter acetylcholirie (ACh) released from the corticopetal projections of the nucleus basalis magnocellularis into primary auditory (A1) and visual (V1) cortices in the rat brain during various Pavlovian associative learning paradigms. The specific aims of these experiments are (1) to demonstrate the relationship between ACh release in task-relevant sensory cortices and the strength of conditioned responding to modality-specific sensory stimuli, (2) to provide evidence for the existence of a differential, regionally-specific pattern of ACh release (as opposed to a generalized, global pattern of release), where the greatest levels of ACh are released in task-relevant sensory cortices during associative learning, and (3) to determine whether manipulating demands on attentional processing of conditioned stimuli causes increases or decreases in the amount of ACh released in the sensory cortex corresponding to the affected conditioned stimulus. These goals will be achieved through a series of three experiments where ACh release will be simultaneously measured in A1 and V1, and where conditioned appetitive approach behavior will be quantified in a classical conditioning paradigm (Experiment 1), an incremental attentional processing paradigm (Experiment 2), or in a blocking paradigm (Experiment 3). Developing this novel model of selective attention and associative learning will provide important insight into the brain mechanisms involved in attention, in cortical synaptic plasticity, and in memory formation itself. Furthermore, results from these experiments will contribute to ongoing research in diverse areas of medicine and neuroscience, ranging from the study of Alzheimer's disease (characterized by cortical ACh deficiency and memory impairments) to reorganization of cortical function following peripheral nerve injury (where such reorganization depends on cortical ACh).

提出的实验涉及使用体内微透析和高性能液体 染色体/电化学检测技术，以测量从底核基核的皮质裂孔突出中释放的神经递质乙酰胆碱（ACH）的量，在各种Pavlovian cossopiative Paradadigmms中，大鼠脑中大鼠脑中大脑中大脑中的脑听觉（A1）和视觉（V1）皮质的含量。这些实验的具体目的是（1）证明与任务相关的感觉皮层中的ACh释放与对模态特异性感觉刺激的有条件响应的强度（2）提供证据，以提供证据证明存在差异，区域特异性的ACh释放模式（相对于广义的全球释放模式） 在关联学习过程中，在与任务相关的感觉皮层中发布，（3）确定对条件刺激的注意处理的需求是否增加或减少了与受影响条件刺激相对应的感觉皮层中释放的ACH量。这些目标将通过一系列三个实验来实现，在这些实验中，将同时在A1和V1中测量ACH的释放，并且将在经典条件范式（实验1）中量化条件的食欲行为，这是一种渐进的注意力处理范式（实验2），或在实验2）或 阻塞范式（实验3）。开发这种新颖的选择性关注和联想学习模型将为您提供重要的洞察力，以了解涉及注意力，皮质突触可塑性和记忆形成本身的大脑机制。此外，这些实验的结果将有助于对医学和神经科学不同领域的持续研究，包括对阿尔茨海默氏病的研究（以皮质ACH缺乏症和记忆力障碍为特征）到外周神经受损后皮质功能的重组（在此重新组织依赖于皮层ACH）。