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 核心B的目的是提供一个足够详细的丘脑皮质相互作用的生物物理模型， 该模型用于指导Thalamus Conte中心的实验，特别是项目P1-P3。该中心是 提出要了解高级丘脑在涉及注意力和决策的任务中的功能， 特别是当感觉输入或上下文存在不确定性时。中心假设是， 灵长类大脑中的丘脑核团，特别是背内侧核（MD）和枕（PUL）， 在整合和门控皮层活动和协调大规模信息流中的基本作用 皮层网络事实上，我们认为，了解大脑皮层认知网络的功能， 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中要做的事情涉及非人类灵长类动物和树鼩，以一种将限制 动力学和功能。此外，该小组还将研究精神分裂症（SZ）的动物模型。 （P3）。在正常和SZ动物模型中，实验者将收集关于脑节律的信息 和尖峰时间的需求。我们的模型还将从健康人类的网络数据中获得信息（P4） 精神分裂症患者（P5）。在堆芯B中构建的计算模型将使用详细的 Hodgkin-Huxley方程的生理框架，受当前和未来数据的约束。的 模型将由多个模块组成，每个模块都有多个单元类型，每个单元都产生多种动力学 在缓慢的时间尺度上有节奏地变化。这些模块中的每一个都可以随着效果而改变 的神经调节，和它们之间的功能连接也受到调制。如此复杂的 模型需要高度约束，我们将使用一种新的方法，其中每个模块都是 受已知生理学的约束，加上它必须用不同的输入产生的多种动力学行为。 该模型的解剖部分是由早期的工作与卡斯特纳解释的作用，多个大脑 在空间注意力任务中的节奏，并表明这些频率在功能上是重要的。持续增 目前的工作，其中的任务要求我们考虑类似的复杂的相互作用，提出了非常普遍的， 重要的问题：这种生物复杂性对功能重要吗？以何种方式？我们假设 已知的复杂节律对功能是必不可少的;在核心B的拟议工作中，我们的目标是阐明 这些动态在需要关注的任务、决策和规则改变方面的重要性。 在目的1中，我们研究了皮质动力学对枕和MD的影响。在目标2中，我们考虑了 在动力学中，当不确定哪一个是线索并且规则中存在切换时。在目标3中， 在精神分裂症的背景下，我们考虑丘脑节律和抑制功能障碍如何导致 认知缺陷，使用目标1和2的工作。这项工作预计将有助于回答 为什么高级丘脑是认知所必需的问题。