Cholinergic Modulation of Cortical Visual Processing

皮质视觉处理的胆碱能调节

• 批准号: 9762906
• 负责人: Monika P. Jadi
• 金额: $ 24.9万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762906
• 关键词: 3-Dimensional; Acetylcholine; Achievement; Address; Affect; Affinity; Anatomy; Animals; Area; Attention; Attention Deficit Disorder; Behavior; Behavioral; Biophysics; Catalogs; Chemicals; Cholinergic Receptors; Complex; Data; Dendrites; Diffuse; Diffusion; Environment; Enzymes; Extracellular Space; Foundations; Functional disorder; GABA Receptor; Goals; Individual; Institutes; Investigation; Ion Channel; Knowledge; Location; Membrane; Memory; Mentors; Modeling; Molecular; Molecular Neurobiology; Morphology; Neurobiology; Neuromuscular Junction; Neurons; Neurosciences; Neurotransmitter Receptor; Neurotransmitters; Output; Pattern; Phase; Physiological; Population; Positioning Attribute; Property; Reaction; Research; Role; Schizophrenia; Second Messenger Systems; Sensory; Shapes; Signal Transduction; Site; Spatial Distribution; Specificity; Structure; Synapses; Synaptic Transmission; System; TBI Patients; Techniques; Testing; Time; Training; Vision research; Visual; Visual Cortex; Visual system structure; Work; area V1; area V4; area striata; attentional modulation; autism spectrum disorder; base; biophysical analysis; biophysical model; career; cell type; cholinergic; computer studies; direct application; experimental study; flexibility; information processing; insight; molecular modeling; nerve supply; network models; neural circuit; neural correlate; neuronal excitability; neuropathology; novel; novel therapeutics; phase change; public health relevance; receptor; receptor expression; relating to nervous system; spatiotemporal; subcellular targeting; tenure track; transmission process; visual processing

DESCRIPTION (provided by applicant): The proposed research combines modeling at molecular, cellular and network scales to address the mechanisms underlying a fundamental behavioral state: attention. Voluntary attention is essential for sensory- guided behavior and memory formation. The neurotransmitter Acetylcholine (ACh) is considered an important contributor to attentional modulation in the cortex. This project aims to understand how the spatio- temporally diffuse ACh system in the cortex achieves spatial and temporal specificity demanded by behavioral tasks such as attention. The studies outlined in this research will broadly aim to test the hypothesis that the cholinergic system achieves the required spatio-temporal precision by coordinating the expression and localization of its molecular components (enzymes, receptors, transporters) rather than the 'classical' approach of precise wiring with fast synaptic transmission. The mentored phase will involve examining how the anatomical organization of the cholinergic system in the cortex shapes the spatio-temporal profile of its transmission. Current models of cholinergic transmission have been implicitly guided by the knowledge of ACh machinery, especially that of enzymatic action, at the neuromuscular junction. Molecular-level models of reaction-diffusion systems will be used to test how the available enzymes in the cortical extracellular space shape the temporal profile of ACh released from non-synaptic sites. The project will aim to generate predictions for the spatial organization of the cholinergic system in the cortical ultra-structure. Inspired by previous work by the candidate, the computational principles guiding the modulatory role of sub-cellular domains of ACh receptors will be investigated in the independent phase. The candidate will use biophysical models of dendrites, ion channels and neurotransmitter receptors for these investigations. The progress made in the mentored and early independent phase will lead to investigation of the mechanisms of cholinergic modulation of network dynamics. Detailed biophysical and phenomenological network models will be used to explore the hypothesis that the known cell-type specificity and sub-cellular patterns of AChR expression in the primary visual cortex underlie the attention-modulation of network oscillations. To achieve these aims the candidate needs further training, specifically in advanced molecular modeling techniques and theoretical foundations of visual and molecular neurobiology. The mentoring lab and the present institute is the ideal training environment for the achievement of these goals. The candidate's mentor is one of the world's pioneers in the computational investigation of neurobiology. The neurobiology division at the institute has a strong focus on vision research. The candidate's main collaborator is one of the leading experts in the cholinergic system in the visual cortex. After a short period n this exciting environment, the candidate expects to be ready to embark upon an independent research career and will seek a tenure-track position in Neuroscience.

描述（由申请人提供）：拟议的研究结合了分子，细胞和网络尺度的建模，以解决基本行为状态：注意力的机制。自觉注意对于感觉引导行为和记忆形成是必不可少的。神经递质乙酰胆碱（ACh）被认为是皮层中注意力调节的重要贡献者。本项目旨在了解皮层的时空弥漫性乙酰胆碱系统如何实现诸如注意力等行为任务所需的空间和时间特异性。本研究概述的研究将广泛地旨在测试这样一种假设，即胆碱能系统通过协调其分子成分（酶、受体、转运体）的表达和定位来实现所需的时空精度，而不是“经典”的快速精确连接方法