CRCNS: Gradients of receptors underlying distributed cognitive functions

CRCNS：分布式认知功能的受体梯度

• 批准号: 9916911
• 负责人: XIAO-JING WANG
• 金额: $ 14.39万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-27 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9916911
• 关键词: 3-Dimensional; Affect; Architecture; Area; Atlases; Base of the Brain; Behavior; Biological; Brain; Brain region; Cell Density; Cells; Characteristics; Chemicals; Code; Cognition; Cognitive; Communities; Complex; Computer Simulation; Data; Data Set; Development; Dimensions; Electrophysiology (science); Ensure; Equilibrium; Fingerprint; Future; Goals; Independent Living; Individual; Instruction; Intelligence; Lead; Link; Macaca; Magnetic Resonance Imaging; Maps; Mathematics; Measures; Mental disorders; Modeling; Monkeys; Motor; National Institute of Mental Health; Neurobehavioral Manifestations; Neuromodulator; Neurosciences; Neurotransmitter Receptor; Parietal; Patients; Pattern; Pharmaceutical Preparations; Research; Resolution; Resources; Scheme; Sensory; Short-Term Memory; Study models; Synapses; System; Testing; Variant; base; cell type; cognitive function; cognitive task; density; information processing; insight; multimodality; neural circuit; neural model; novel; organizational structure; programs; receptor; receptor density; receptor function; relating to nervous system; sensory system; success

A key goal of the NIMH is to define the mechanisms of complex behaviors. This necessitates an approach that spans biological scales, but we have been lacking a single theoretical framework that links neurotransmitter receptor function, large-scale patterns of brain activity and cognition. Working memory is a key building block of cognition, but our understanding of why working memory emerges in sorne parts of cortex, but not others, is limited. The macaque is an important model for studying higher cognitive function with relevance to psychiatric disease, due to their intelligent behavior and relatively similar brains. We propose the creation of a high-resolution 3D atlas of the macaque brain, and use it to create data-driven neural circuit models that will give us key insights into the relationship between regional variations in receptor densities and the emergence of distributed working memory. The atlas will enable quantification of the regional and laminar distribution of 14 types of receptors (receptor fingerprints) and cell densities across the entire macaque cortex. This will allow for interrogation of receptor fingerprints and cell densities with submillimeler precision. It will be accompanied by a novel parcellation scheme based on the gradients of cyto- and receptor-architecture across cortex. This atlas will be registered lo the NIMH Macaque Template for easy integration with macaque /MRI data. We will identify the principal gradients that underlie the distribution of receptors across cortex and compare these to hierarchies of sensory systems and cognitive networks using open-access laminar tract-tracing and /MRI data. This approach will uncover the receptor signature underlying distinct functional hierarchies. We will use the idea of bifurcations from mathematics to interrogate how changes lo the density of receptors across cortex may lead to the emergence of working-memory like persistent activity in particular regions of cortex. Crucially, we will allow the experimentally measured receptor densities lo scale the effects of each receptor in each cortical area and layer. We hypothesize that the pattern of working memory activity observed across cortical areas and lamina depends critically on the regional distribution of the receptors. Further, we will expand our model to include inter-areal connectivity data and investigate how release of neuromodulators can shift cortical activity between cognitive networks. The results of our proposed research are likely to significantly advance this area of research, with broad implications. The highly promising preliminary results have confirmed the validity of the approach, ensuring that all aspects of the program have a high likelihood of success. RELEVANCE (See instructions): Cognitive symptoms of mental illnesses are difficult to treat, but can be the biggest impediment to patients living independently. Cognitive functions rely on many brain areas communicating through chemicals and receptors, which are affected by mental illness and medication. We will map the pattern of these receptors in the brain, so we can build computer models to understand why cognitive functions differ across brain regions. This could lead to the development of new treatments for cognitive symptoms in mental illness.

NIMH的关键目标是定义复杂行为的机制。这需要一种方法 这跨越了生物学量表，但是我们缺少一个链接的一个理论框架 神经递质受体功能，大脑活动和认知的大规模模式。工作记忆是一个 认知的关键构件，但是我们对为什么工作记忆出现的理解在 皮质，但没有其他是有限的。猕猴是研究较高认知功能的重要模型 由于其智能行为和相对相似的大脑，与精神病有关。我们 提出创建猕猴大脑的高分辨率3D地图集，并使用它来创建数据驱动 神经电路模型将使我们对区域变化之间关系的关键见解 受体密度和分布式工作记忆的出现。地图集将实现量化 14种类型的受体（受体指纹）和细胞密度的区域和层流分布 在整个猕猴的皮质中。这将允许对受体指纹和细胞密度的询问 具有亚略列精度。它将伴随着基于梯度的新型分割方案 跨皮质的细胞和受体结构。该地图集将注册为NIMH猕猴 模板，可轻松与猕猴 /MRI数据集成。我们将确定基于的主要梯度 受体在跨皮质的分布，并将其与感觉系统的层次结构和 使用开放式层流式追踪和 /MRI数据的认知网络。这种方法将发现 受体签名基础不同的功能层次结构。我们将使用分叉的想法 数学以询问如何变化LO跨皮质的受体密度可能导致 在皮质的特定区域中的工作记忆的出现。至关重要的是，我们将允许 实验测量的受体密度lo缩放每个受体在每个皮质区域的影响 和层。我们假设在皮质区域内观察到的工作记忆活动的模式以及 薄片批判性地取决于受体的区域分布。此外，我们将把模型扩展到 包括美地连通性数据并研究神经调节剂的释放如何转移皮质 认知网络之间的活动。我们拟议的研究的结果可能会大大提高 这一研究领域具有广泛的影响。高度有希望的初步结果证实了 该方法的有效性，确保该计划的所有方面都具有很高的成功。 相关性（请参阅说明）： 精神疾病的认知症状很难治疗，但可能是患者的最大障碍 独立生活。认知功能依赖于许多通过化学物质通信的大脑区域 受体，受到精神疾病和药物的影响。我们将绘制这些受体的模式 在大脑中，我们可以构建计算机模型以了解为什么认知功能在大脑中有所不同 地区。这可能导致发展精神疾病认知症状的新疗法。