Cholinergic Mechanisms in Spatial Attention

空间注意力的胆碱能机制

• 批准号: 8841464
• 负责人: Anita A Disney
• 金额: $ 24.9万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8841464
• 关键词: Acetylcholine; Achievement; Address; Affect; Agonist; Anatomy; Area; Arousal; Attention; Attention deficit hyperactivity disorder; Attentional deficit; Autistic Disorder; Award; Axon; Basic Science; Behavioral; Behavioral Model; Biological Sciences; Caliber; Cells; Chemicals; Cholinergic Receptors; Clinical; Cognition; Cognitive; Cognitive deficits; Complement; Data; Dementia; Disease; Electric Stimulation; Employee Strikes; Environment; Etiology; Event; Failure; Fostering; Foundations; Functional disorder; Genetic; Goals; Human; Impairment; Institutes; Intervention; Learning; Measures; Mediating; Mental disorders; Mentors; Methods; Modeling; Mood Disorders; Mus; Neuromodulator; Neurons; Neurosciences; Perception; Pharmacology; Phase; Photic Stimulation; Physiological; Physiology; Positioning Attribute; Primates; Process; Protocols documentation; Receptor Cell; Research; Resolution; Rodent; Role; Schizophrenia; Sensory Process; Specificity; Structure; System; Techniques; Technology; Testing; Time; Tissues; Training; Work; abstracting; area MT; area V1; awake; basal forebrain; base; career; cell type; cholinergic; clinical practice; cognitive function; executive function; gamma-Aminobutyric Acid; in vivo; information processing; innovation; insight; mouse model; neocortical; neuropathology; nonhuman primate; optogenetics; planetary Atmosphere; public health relevance; receptor; receptor function; research study; selective attention; sensory cortex; skills; stimulus processing; stimulus sensitivity

Abstract Studying the normal functions and mechanisms of perception and attention is essential to identifying and understanding the failures in information processing and cognition that are aspects of many neuropathologies. Cognitive and attentional deficits are seen in a number of mental illnesses including schizophrenia, mood disorders and dementias of varying etiology. Studies in rodents suggest that acetylcholine (ACh) mediates attention, and cholinergic dysfunction is implicated in many cognitive neuropathologies. Questions arise, however, when one tries to model the cholinergic system as the basis for spatially precise attentional effects such as have been demonstrated in humans and non-human primates (NHPs). Specifically, the smallest piece of 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 attention in primates. Thus, while rodent studies have contributed much to our understanding of cholinergic processes, investigating cholinergic function in a species in which attention and arousal are more separable in behavioral tasks is essential. Also necessary, if we are to build the detailed mechanistic descriptions necessary to drive innovation in clinical practice, is a thorough understanding of cholinergic action in cortical circuits. Currently, our progress is hampered by a striking lack of circuit-level data regarding the structure and function of the cholinergic system and by a limited understanding of the behavioral drivers of ACh release. The work I propose to conduct during the mentored and independent phases of this award will address these gaps by 1) using anatomical techniques to provide quantitative data on ACh receptor localization in cortical areas modulated by attention (both phases), 2) using optogenetic techniques to examine the effect that naturalistic ACh release has on the processing of sensory input by a local cortical circuit in vivo (mentored phase), and 3) using high-resolution chemical sensing to determine the spatial profile of ACh release in the sensory cortex of a) the anesthetized rodent under optogenetic control (mentored phase) and b) the awake, behaving NHP during an attention task (both phases). To achieve these aims I need further training that will complement my existing skills in anatomy, physiology and pharmacology. Specifically, I need to learn how to train and record from NHPs that are engaged in tasks which probe attentional function. I also need a protected and innovative environment to work in while I develop protocols for chemical sensing in vivo in the behaving NHP. The Salk Institute is the ideal training environment for the achievement of these goals. Dr. John Reynolds, my mentor, is one of the world's foremost experts on the physiology of attention in NHPs and has a vibrant lab in which innovation is a normal part of the approach to research. The Salk Institute is also renowned for a collaborative atmosphere that fosters innovative approaches in the biological sciences. After a short period in this exciting environment, I expect to be ready to embark upon an independent research career and will seek a tenure-track position in Neuroscience.

抽象的 研究正常功能和感知和注意力的机制对于识别和 了解信息处理和认知的失败，这是许多神经病理学的方面。 认知和注意力缺陷在许多精神疾病，包括精神分裂症，情绪 不同病因的疾病和痴呆症。啮齿动物的研究表明乙酰胆碱（ACH）介导 注意和胆碱功能障碍与许多认知神经病理学有关。出现问题， 但是，当人们试图建模胆碱能系统作为空间精确的注意效果的基础 如在人类和非人类灵长类动物（NHP）中所证明的。具体而言，最小的一块 可以通过ACH独立调节的组织可能太大，以至于允许在地形上 精确的加工加工似乎是灵长类动物关注的基础。因此，啮齿动物研究 为我们对胆碱能过程的理解做出了很大的贡献，研究了胆碱能的功能 在行为任务中，注意力和唤醒更可分离的物种至关重要。也有必要，如果 我们要构建在临床实践中推动创新所需的详细机械描述，这是一个 对皮质回路中胆碱能作用的透彻理解。目前，我们的进度受到了 缺乏有关胆碱能系统结构和功能的电路级数据以及有限的 了解ACH释放的行为驱动因素。我建议在指导期间进行的工作 该奖项的独立阶段将通过1）使用解剖技术来解决这些差距 有关注意的皮质区域中ACH受体定位的定量数据（两阶段），2）使用 光遗传技术以检查自然主义ACH对感觉的处理的影响 由局部皮质电路在体内输入（指导阶段），3）使用高分辨率化学传感 确定A）在A）的感觉皮层中ACH释放的空间曲线 光遗传控制（指导阶段）和b）醒着，在注意任务（两个阶段）中行为NHP。 为了实现这些目标，我需要进一步的培训，以补充我现有的解剖学，生理学的技能 和药理学。具体来说，我需要学习如何向从事任务的NHP培训和记录 哪个探测注意功能。我还需要一个受保护和创新的环境才能在我开发时工作 在表现NHP中体内化学传感的方案。 Salk Institute是理想的培训环境 为了实现这些目标。我的导师约翰·雷诺兹（John Reynolds）博士是世界上最重要的专家之一 NHP中关注的生理学，并具有一个充满活力的实验室，其中创新是方法的正常部分 进行研究。 Salk Institute还以一种促进创新的协作氛围而闻名 生物科学的方法。在这个令人兴奋的环境中短暂的一段时间之后，我希望已经准备好 开始独立的研究职业，并将在神经科学中寻求终身任职地位。