Cholinergic mechanisms in visual spatial attention

视觉空间注意力的胆碱能机制

• 批准号: 8003894
• 负责人: Anita A Disney
• 金额: $ 2.38万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8003894
• 关键词: Acetylcholine; Address; Alzheimer' s Disease; Area; Arousal; Attention; Attention deficit hyperactivity disorder; Behavioral; Biological; Chemicals; Cholinergic Receptors; Cognitive; Data; Dementia; Employee Strikes; Extinction (Psychology); Failure; Human; Lip structure; Macaca; Mammals; Modeling; Process; Resolution; Rodent; Schizophrenia; Sensory Process; Staging; Structure; System; Techniques; Technology; Tissues; Vision; Visual Cortex; Visual Pathways; Visual attention; Visuospatial; Work; age related; awake; base; cholinergic; directed attention; in vivo; neglect; neuroregulation; nonhuman primate; public health relevance; visual stimulus

DESCRIPTION (provided by applicant): Studies in rodents have suggested that the acetylcholine (ACh) is an essential component of the biological basis for directed attention. Questions arise, however, when one tries to model the cholinergic system as the basis for spatially and temporally precise attentional effects such as have been demonstrated in human and non-human primates. For example the smallest piece of cortical tissue which can be independently modulated by ACh may be too large to allow for the topographically precise enhancement of processing which appears to underlie attentional mechanisms. Studying cholinergic neuromodulation in a species where attention and arousal are more easily separable in behavioral tasks is essential, however such a move is hampered by a striking lack of circuit-level data regarding the structure and function of the cholinergic system in higher mammals. The proposed work will address this gap by 1) using anatomical techniques in the macaque to provide large-scale quantitative data on ACh receptor localization in cortical areas known to be involved in or modulated by attention (e.g. V4, MT and LIP), 2) using optogenetic techniques in rodents to examine the effect that naturalistic ACh release has on the processing of a visual stimulus at various stages of the visual pathway in vivo, and 3) using a high-resolution chemical sensing technique to determine the spatial and temporal profile of acetylcholine release in the visual cortex of the a) anesthetized rodent under optogenetic control and of the b) awake-behaving nonhuman primate during an attention task. PUBLIC HEALTH RELEVANCE: We will use cutting-edge technology to elucidate the function of acetylcholine in vision and visual attention. Abnormal cholinergic modulation is strongly implicated in age-related dementias including Alzheimer's disease (AD) and associated failures of vision and selective visual attention. Understanding how acetylcholine subserves normal cognitive and sensory processing will help elucidate which aspects of the deficits seen in AD are related to loss of cholinergic function and will also aid in understanding related deficits of attention, including attentional failures associated with Schizophrenia, neglect, extinction and Attention-Deficit- Hyperactivity-Disorder (ADHD).

描述（由申请人提供）：啮齿动物的研究表明，乙酰胆碱（ACH）是定向注意的生物学基础的重要组成部分。但是，当人们试图对胆碱能系统建模为空间和时间上精确的注意效果的基础时，就会出现问题。例如，可以通过ACH独立调节的最小的皮质组织可能太大，无法在地形上精确的加工增强，这似乎是注意力的基础。在行为任务中更容易分离的物种中，研究胆碱能神经调节是必不可少的，但是由于缺乏有关高级哺乳动物胆碱能系统的结构和功能的令人震惊的电路级别数据，这种举动受到了阻碍。拟议的工作将通过1）在猕猴中使用解剖技术来解决这一差距，以提供有关ACh受体定位的大规模定量数据，该数据在皮质区域中所涉及或调节的皮质区域中定位，例如V4，MT和LIP和LIP和LIP），2），2），2），2），2），使用啮齿动物的启用，以启动的效果，以相互启动的效果，以进行自然的ACH释放。 3）使用高分辨率的化学传感技术来确定乙酰胆碱释放在A）在光遗传学控制下和B）注意事项期间在光遗传学控制下的麻醉啮齿动物的视觉皮层中的空间和时间谱。 公共卫生相关性：我们将使用尖端技术来阐明乙酰胆碱在视觉和视觉关注中的功能。异常的胆碱能调节与年龄相关的痴呆症（包括阿尔茨海默氏病（AD）以及视力和选择性视觉关注的相关失败）极大地涉及。了解乙酰胆碱如何在正常的认知和感觉处理中辅助如何有助于阐明AD中看到的缺陷的哪些方面与胆碱能功能的丧失有关，还将有助于理解关注的相关缺陷，包括与精神分裂症，忽视，疏忽和注意力缺陷 - 缺乏症状 - 弱点 - 超级活跃率相关的注意力失败）。