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CRCNS: Gradients of receptors underlying distributed cognitive functions

CRCNS：分布式认知功能的受体梯度

基本信息

批准号：
10251904
负责人：
XIAO-JING WANG
金额：
$ 15.6万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
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/10251904
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 Models 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

项目摘要

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 的一个关键目标是定义复杂行为的机制。这就需要一种方法跨越生物尺度，但我们一直缺乏一个单一的理论框架来链接神经递质受体功能、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组成部分，但我们对为什么工作记忆出现在某些部分的理解皮层（而非其他皮层）是有限的。猕猴是研究高级认知功能的重要模型由于他们的聪明行为和相对相似的大脑，与精神疾病相关。我们提议创建猕猴大脑的高分辨率 3D 图集，并用它来创建数据驱动的神经回路模型将为我们提供关于区域差异之间关系的重要见解受体密度和分布式工作记忆的出现。该图集将能够量化 14种受体（受体指纹）的区域和层状分布以及细胞密度遍布整个猕猴皮层。这将允许询问受体指纹和细胞密度具有亚毫米级精度。它将伴随着一种基于梯度的新颖的分割方案跨皮质的细胞和受体结构。该图集将在 NIMH 猕猴注册可轻松与猕猴/MRI 数据集成的模板。我们将确定背后的主要梯度受体在整个皮层的分布并将其与感觉系统的层次结构进行比较使用开放访问层流追踪和/MRI 数据的认知网络。这种方法将揭示不同功能层次结构背后的受体特征。我们将使用分叉的想法数学来探究皮层受体密度的变化如何导致工作记忆的出现，就像皮层特定区域的持续活动一样。至关重要的是，我们将允许实验测量的受体密度可以衡量每个皮质区域中每个受体的影响和层。我们假设在皮质区域观察到的工作记忆活动模式层主要取决于受体的区域分布。此外，我们将把我们的模型扩展到包括区域间连接数据并研究神经调节剂的释放如何改变皮质认知网络之间的活动。我们提出的研究结果可能会显着推进这一研究领域具有广泛的影响。非常有希望的初步结果证实了该方法的有效性，确保该计划的各个方面都有很高的成功可能性。相关性（参见说明）：精神疾病的认知症状很难治疗，但可能是患者最大的障碍独立生活。认知功能依赖于许多大脑区域通过化学物质和受体，受精神疾病和药物的影响。我们将绘制这些受体的模式图在大脑中，所以我们可以建立计算机模型来理解为什么认知功能在大脑中存在差异地区。这可能会导致针对精神疾病认知症状的新疗法的开发。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cytoarchitectonic, receptor distribution and functional connectivity analyses of the macaque frontal lobe.

DOI：
10.7554/elife.82850
发表时间：
2023-08-14
期刊：
eLife
影响因子：
7.7
作者：
Rapan L;Froudist-Walsh S;Niu M;Xu T;Zhao L;Funck T;Wang XJ;Amunts K;Palomero-Gallagher N
通讯作者：
Palomero-Gallagher N

Organization of the macaque monkey inferior parietal lobule based on multimodal receptor architectonics.