Computational Core

项目总结 核心B的目标是提供足够详细的丘脑皮质相互作用的生物物理模型，以便 该模型用来指导丘脑Conte中心的实验，特别是投影P1-P3。中心是 建议理解高阶丘脑在涉及注意力和决策的任务中的功能， 尤其是当感觉输入或背景存在不确定性时。中心假设是更高阶的 在灵长类动物大脑中的丘脑核团，特别是背内侧核(MD)和枕核(PUL)，发挥着重要的作用 在整合和控制皮质活动以及协调大范围信息流动方面的基础作用 大脑皮层网络。事实上，我们提出，对大脑皮质认知网络功能的理解 如果不了解皮层和丘脑的相互作用，灵长类动物的大脑是不可能的。这些实验 将在P1-P3中完成的涉及非人灵长类和树鼠的方式将限制电路模型 既有动力也有功能。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，实验者都会收集有关大脑节律的信息 以及模型所需的扣球时间。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)。要在核心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限制。这个 模型将使用多个模块构建，每个模块具有多种细胞类型，每个模块产生多种类型的动力学 它们本身可以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效果而变化 它们之间的功能联系也受到调制的影响。这样一种情结 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 受制于已知的生理学，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与卡斯特纳一起解释多个大脑的作用的工作所推动的 空间注意任务中的节律，并表明这些频率在功能上是重要的。事实上， 目前的工作，其中的任务要求我们考虑类似的复杂相互作用，提出了非常普遍的和 重要的问题：这种生物复杂性对功能重要吗？以什么方式？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 在需要注意、决策和改变规则的任务背景下，这些动态的方式是重要的。 在目标1中，我们研究了皮质动力学对枕骨和MD的影响。在目标2中，我们考虑了这些变化 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Aim3中，在 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是如何导致 认知缺陷，使用目标1和2的工作。这项工作有望有助于回答 为什么认知需要高级丘脑的问题。

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.