Functional diversity of cholinergic streams modulating cognition

胆碱能流调节认知的功能多样性

• 批准号: 9151636
• 负责人: Bernardo Rudy
• 金额: $ 25.43万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9151636
• 关键词: Acetylcholine; Affect; Alzheimer' s Disease; Animal Model; Arousal; Attention; Behavior; Behavioral; Brain; Cells; Cellular Morphology; Cholinergic Agents; Cognition; Correlation Studies; Data; Databases; Dementia; Detection; Disease; Functional disorder; Goals; Grant; Health; Heterogeneity; Human; Impairment; Individual; Knowledge; Label; Memory; Methodology; Methods; Minority; Morphology; Neocortex; Neurons; Parkinson Disease; Pattern; Performance; Process; Reporting; Role; Schizophrenia; Sensory; Shapes; Specificity; Stream; System; Testing; Time; Work; alertness; basal forebrain; basal forebrain cholinergic neurons; base; cholinergic; cholinergic neuron; cognitive function; cognitive process; human disease; in vivo; memory process; neocortical; nerve supply; nervous system disorder; novel; optogenetics; research study; sensory gating; spatiotemporal

 DESCRIPTION (provided by applicant): The cholinergic system has critical roles in arousal, alertness, attention, sensory gating and memory processes. Moreover, impairments of the cholinergic system have been associated with human disease, including the dementia of Alzheimer's and Parkinson diseases. However, in spite of the importance of acetylcholine (ACh) for normal cognitive function and its potential significance in disease, the functional organizatio of the neurons providing cholinergic projections to the neocortex, and the circuit and cellular mechanisms by which ACh regulates specific cortical functions are poorly understood. These data are necessary to shape functional descriptions of the cholinergic system in cognitive processes, and advance the mechanistic analysis of its dysfunction in disease. Recent evidence suggests that cholinergic cells in the basal forebrain have diverse and specific patterns of innervation of the cortex. The working hypothesis of this proposal is that distinct cholinergic streams have different activity profiles during behavior thus establishing a spatiotemporal division of labor for the modulation of cognitive processes. In order to test this hypothesis, and more generally to understand the functional organization of the cholinergic system, it is necessary to correlate the activity patterns of individual cholinergic neurons during the performance of a cholinergic-dependent behavioral task with their cortical axonal innervation. However, due to the fact that cholinergic cells represent a minority of the neurons in the basal forebrain, it has been extremely difficult to record specifically from cholinergic cells in vivo, ad the activity of cholinergic neurons in task-related contexts has not been reported. In this exploratory grant we will utilize a novel method known as "channelrhodopsin-assisted patching" to record and label cholinergic cells in the basal forebrain during the execution of a sensory detection task, in order to investigate the correlation between the activity profile of cholinergic neurons during a behavioral task and their pattern of innervation of the cortex, with the goal of obtaining evidence in support of our working hypothesis. The experiments will provide for the first time information about the activity of cholinergic neurons with specific patterns of cortical innervation during a behavioral task, and produce a large database of individual, complete cholinergic cell morphologies for a more thorough description of the anatomical and functional organization of the basal forebrain cholinergic projection system.

 描述（由适用提供）：胆碱能系统在唤醒，警觉性，注意力，感觉门控和记忆过程中具有关键作用。此外，胆碱能系统的损害与人类疾病有关，包括阿尔茨海默氏症和帕金森氏病的痴呆症。然而，尽管乙酰胆碱（ACH）对正常认知功能的重要性及其在疾病中的潜在意义，但神经元的功能组织为新皮层提供了胆碱能项目，而ACH调节特定皮质功能的电路和细胞机制也很差。这些数据对于在认知过程中塑造胆碱能系统的功能描述是必要的，并推进其疾病功能障碍的机械分析。最近的证据表明，基本前脑中的胆碱能细胞具有潜水员和皮质神经支配的特定模式。该提议的工作假设是，在行为过程中，不同的胆碱能流具有不同的活性特征，从而建立了劳动的空间时间分割以调节认知过程。为了检验这一假设，更普遍地了解胆碱能系统的功能组织，在执行胆碱能依赖性行为任务的过程中，有必要将单个胆碱能神经元的活性模式与皮质轴突支架相关联。但是，由于胆碱能细胞代表基本前脑中的少数神经元，因此很难从体内胆碱能细胞进行专门记录，因此尚未报告与任务相关的上下文中胆碱能神经元的活性。在这项探索性赠款中，我们将利用一种称为“ ChannelRhopopsin辅助补丁”的新方法在执行感官检测任务期间记录和标记基本前脑中的胆碱能细胞，以研究胆碱能曲线的相关性 在行为任务中的神经元及其对皮层神经支配的模式，目的是获得支持我们工作假设的证据。该实验将提供有关胆碱能神经元活动的首次信息，具有皮质的特定模式 行为任务期间的神经支配，并产生一个大的单个，完整的胆碱能细胞形态的数据库，以对基本前脑胆碱能投影系统的解剖学和功能组织进行更彻底的描述。