Validating Theoretical Models with Neurophysiology and Optogenetics

用神经生理学和光遗传学验证理论模型

• 批准号: 10438696
• 负责人: Hillel Adesnik
• 金额: $ 37.22万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10438696
• 关键词: 3-Dimensional; Calcium; Cells; Dimensions; Fire - disasters; Foundations; Goals; Image; Individual; Laws; Membrane Potentials; Modeling; Monitor; Neurons; Optics; Outcome; Photic Stimulation; Photons; Research Project Grants; Resolution; Stimulus; Technology; Testing; Theoretical model; V1 neuron; cell type; experimental study; improved; in vivo; insight; millisecond; movie; neural circuit; neurophysiology; new technology; novel; novel strategies; optogenetics; photoactivation; predictive modeling; preference; relating to nervous system; response; retinotopic; theories

ABSTRACT Theoretical models of neural circuits aim to provide a set of fundamental principles that capture neural dynamics and explain neural computation. While their value scales with the range of dynamics they can capture and explain, the models’ validity depends on their ability to make accurate predictions in the face of defined perturbations. The goal of this specific research project is to employ defined perturbations that definitively test core predictions of the new models. Unquestionably, the most powerful approach for perturbing neural activity is optogenetics, yet one photon optogenetics is not up to the task. Therefore, we will use a novel all-optical multiphoton approach that combines calcium imaging with multiphoton holographic optogenetics. This new technology allows large ensembles of neurons to be targeted with single cell resolution for photo-activation in three dimensions. Using this new approach, we will test a concerted set of concrete predictions with extremely well-defined perturbations, that were never before possible. These optogenetic perturbations thus close the loop of iterative model refinement and testing to arrive at the most powerful and predictive model yet of any cortical circuit.

抽象的 神经回路的理论模型旨在提供一组捕获神经动态的基本原理 并解释神经计算。尽管它们的价值尺度与可以捕获的动态范围范围 解释，模型的有效性取决于他们在定义的情况下做出准确预测的能力 扰动。该特定研究项目的目的是采用明确测试的定义扰动 新模型的核心预测。毫无疑问，神经活动的最强大方法是 光遗传学，但是一种光子光遗传学并不符合任务。因此，我们将使用小说全光 多光子方法将钙成像与多光子全息光遗传学结合在一起。这个新 技术允许将大型神经元组成以单细胞分辨率为目标，以进行光激活 三个维度。使用这种新方法，我们将测试一套一致的混凝土预测 定义明确的扰动，从来没有做过。这些光遗传扰动因此关闭了循环 迭代模型的完善和测试，以达到任何皮质的最强大和最预测的模型 电路。