Computational Core

计算核心

• 批准号: 10633811
• 负责人: NANCY KOPELL
• 金额: $ 34.55万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-03 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633811
• 关键词: Acetylcholine; Affect; Anatomic Models; Animal Model; Attention; Behavior; Behavioral; Biological; Biophysics; Brain; Cells; Cognition; Cognitive; Cognitive deficits; Complex; Computer Models; Coupled; Cues; Data; Decision Making; Detection; Dimensions; Environment; Equation; Frequencies; Functional disorder; Future; Glutamates; Hodgkin-Huxley model; Human; Impaired cognition; Learning; Medial Dorsal Nucleus; Methodology; Modeling; Motivation; Motor Neurons; Neuromodulator; Neurons; Output; Patients; Performance; Periodicals; Periodicity; Phase; Physiological; Physiology; Play; Primates; Property; Pulvinar structure; Reticular Cell; Role; Sampling; Schizophrenia; Sensory; Signal Transduction; Testing; Thalamic Nuclei; Thalamic structure; Theta Rhythm; Time; Tupaiidae; Uncertainty; Variant; Visual; Work; behavior prediction; behavioral outcome; biophysical model; cell type; cognitive control; experimental study; information gathering; neural; neuroregulation; nonhuman primate; novel; response; sensory input; sensory integration; spelling; sustained attention; synergism; visual motor

Project summary The aim of Core B is to provide an adequately detailed biophysical model of thalamocortical interactions to allow the model to guide experiments of the Thalamus Conte Center, especially Projects P1-P3. The Center is proposing to understand the function of higher-order thalamus in tasks involving attention and decision making, particularly when there are uncertainties in sensory input or context. The Center hypothesis is that higher-order thalamic nuclei in the primate brain, particularly the mediodorsal nucleus (MD) and the pulvinar (PUL), play a fundamental role in integrating and gating cortical activity and coordinating information flow across large-scale cortical networks. Indeed, we propose that an understanding of the functioning of cortical cognitive networks in the primate brain is not possible without understanding the interactions of cortex and thalamus. The experiments to be done in P1-P3 involve non-human primates and tree shrews in a way that will constrain circuit models of both dynamics and function. In addition, the group will also investigate animal models of schizophrenia (SZ) (P3). In both the normal and SZ animal models, the experimentalist will gather information about brain rhythms and spike timing need for the model. Our model will also be informed by network data from healthy humans (P4) and Schizophrenia patients (P5). The computational model to be constructed in core B will use the detailed physiological framework of Hodgkin-Huxley equations, constrained by currently available and future data. The model will be built with multiple modules, each with multiple cell types, each producing multiple kinds of dynamics that can themselves change rhythmically on a slow time scale. Each of these modules can change with effects of neuromodulation, and the functional connections among them are also subject to modulation. Such a complex model needs to be highly constrained, and we will make use of a novel methodology in which each module is constrained by known physiology plus the multiple dynamical behaviors that it must produce with different inputs. The anatomy of the model is partly motivated by earlier work with Kastner explaining the roles of multiple brain rhythms in a spatial attention task and showing that those frequencies are functionally important. Indeed, the current work, in which the tasks require us to consider similarly complex interactions, raises the very general and important question: Is such biological complexity important for function, and in what ways? We hypothesize that the known complex rhythms are essential to function; in the proposed work of Core B, we aim to spell out in what ways those dynamics are important in the context of tasks requiring attention, decision making and rule changing. In Aim 1, we investigate the effects of cortical dynamics on pulvinar and MD. In Aim 2, we consider the changes in dynamics when there is uncertainty about which is the cue and there is switching in the rule. In Aim3, in the context of schizophrenia, we consider how dysfunctions in thalamic rhythms and in inhibitory function can lead to cognitive deficits, using the work of Aims 1 and 2. This work is expected to contribute to answers to the question of why the higher order thalamus is needed for cognition.

项目摘要 核B的目的是提供丘脑皮质相互作用的充分详细的生物物理模型，以允许 指导Thalamus Conte中心的实验的模型，尤其是Project P1-P3。中心是 建议了解高阶丘脑在涉及注意和决策的任务中的功能， 特别是当感觉输入或上下文中存在不确定性时。中心假设是高阶 灵长类动物大脑中的丘脑核，尤其是中正核（MD）和pulvinar（pul），播放 在整合和门控皮质活动和协调大规模的信息流中的基本作用 皮质网络。确实，我们建议对皮质认知网络功能的理解 如果不了解皮质和丘脑的相互作用，灵长类动物的大脑是不可能的。实验 在P1-P3中进行的涉及非人类灵长类动物和树sh，以限制电路模型的方式 动力和功能。此外，该小组还将研究精神分裂症的动物模型（SZ） （P3）。在正常动物模型和SZ动物模型中，实验者将收集有关大脑节奏的信息 和模型的尖峰时序需要。我们的模型还将通过健康人的网络数据（P4）告知 和精神分裂症患者（P5）。核心B中要构建的计算模型将使用详细的 Hodgkin-Huxley方程的生理框架，受当前可用数据和未来数据的约束。这 模型将使用多个模块构建，每个模块都有多种单元格类型，每种模块都会产生多种动力学 这本身可以在缓慢的时间范围内进行节奏。这些模块中的每一个都可以随效果而变化 神经调节以及它们之间的功能连接也受到调节​​。如此复杂 模型需要受到高度限制，我们将利用一种新方法，每个模块是 受已知生理学以及必须用不同输入产生的多种动态行为的限制。 该模型的解剖学部分是由与卡斯特纳（Kastner）早期工作解释了多个大脑的作用的动机 在空间注意任务中的节奏，并表明这些频率在功能上很重要。确实， 当前的工作，任务要求我们考虑类似复杂的互动，并提高了一般性的互动 重要问题：这种生物学复杂性对功能以及哪种方式重要？我们假设这一点 已知的复杂节奏对于功能至关重要。在核心B的拟议工作中，我们的目标是阐明 这些动态在需要注意，决策和规则改变的任务中很重要。 在AIM 1中，我们研究了皮质动力学对Pulvinar和MD的影响。在AIM 2中，我们考虑更改 在动态中，当存在提示的不确定性时，规则中有切换。在AIM3中 精神分裂症的背景，我们考虑丘脑节奏和抑制功能中的功能障碍如何 使用AIM 1和2的工作，以认知缺陷。这项工作有望有助于答案 为什么需要高阶丘脑才能进行认知的问题。