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）：对啮齿动物的研究表明，乙酰胆碱（ACh）是定向注意力的生物学基础的重要组成部分。然而，当人们试图将胆碱能系统建模为空间和时间精确注意力效应的基础时，问题就出现了，正如在人类和非人类灵长类动物中所证明的那样。例如，可由乙酰胆碱独立调节的最小皮质组织可能太大，无法实现地形上精确的处理增强，而处理似乎是注意力机制的基础。研究在行为任务中注意力和唤醒更容易分离的物种的胆碱能神经调节是至关重要的，然而，由于严重缺乏有关高等哺乳动物胆碱能系统结构和功能的回路级数据，这一举措受到阻碍。拟议的工作将通过以下方式解决这一差距：1）在猕猴中使用解剖技术，提供已知参与注意力或受注意力调节的皮质区域（例如V4、MT和LIP）中乙酰胆碱受体定位的大规模定量数据，2）在啮齿类动物中使用光遗传学技术来检查自然乙酰胆碱释放对体内视觉通路各个阶段视觉刺激处理的影响，以及 3) 使用高分辨率化学传感技术来确定 a) 在光遗传学控制下的麻醉啮齿动物和 b) 在注意力任务期间表现清醒的非人类灵长类动物的视觉皮层中乙酰胆碱释放的空间和时间分布。 公共健康相关性：我们将使用尖端技术来阐明乙酰胆碱在视力和视觉注意力中的功能。异常的胆碱能调节与年龄相关的痴呆症密切相关，包括阿尔茨海默病（AD）以及相关的视力和选择性视觉注意力障碍。了解乙酰胆碱如何促进正常的认知和感觉处理将有助于阐明 AD 中的哪些方面的缺陷与胆碱能功能丧失有关，也有助于理解相关的注意力缺陷，包括与精神分裂症、忽视、消退和注意力缺陷多动障碍 (ADHD) 相关的注意力缺陷。