Validating Theoretical Models with Neurophysiology and Optogenetics

摘要 神经回路的理论模型旨在提供一套捕捉神经动力学的基本原理 并解释神经计算。虽然它们的价值随着它们可以捕获的动态范围而扩展 解释说，模型的有效性取决于它们在面对定义的 微扰。这个特定研究项目的目标是使用定义的微扰来确定测试 新车型的核心预测。毫无疑问，扰乱神经活动的最有效方法是 光遗传学，然而单光子光遗传学不能胜任这项任务。因此，我们将使用一种新颖的全光 结合钙成像和多光子全息光遗传学的多光子方法。这是一项新的 技术允许以单个细胞分辨率针对大的神经元集合进行光激活 三个维度。使用这种新方法，我们将测试一组协调一致的具体预测，其中包括 定义明确的扰动，这在以前是不可能的。这些光遗传微扰因此闭合了环路 迭代模型的改进和测试，以得出迄今为止最强大和最具预测性的皮质模型 巡回赛。

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.