Models of visual cortical circuitry and development

描述（由申请人提供）：我们试图了解视觉皮层的电路，其活动依赖性发展的规则，以及这些辅助的计算功能。这些理解对于我们理解正常视力和包括弱视和斜视在内的中枢性疾病都至关重要。我们将V1作为一个模型系统。我们使用建模来测试连贯的假设，以V1功能性反应特性和可塑性规则的电路基础电路的发展。建模允许测试电路结构和/或开发规则的综合图片对各种实验结果和开发新的和未预料到的测试的图片。本课题的具体目标是：（1）建立具有生物学可识别性和可测试性的成熟视皮层神经回路模型。特别是，我们将测试的假设（i），细胞内以及细胞外的经典RF响应在LGN受体V1简单的细胞，包括对比度依赖性降低电压噪声是关键的对比度不变的方向调整，可以从简单的，基本上前馈模型定量理解。(ii)LGN受体V1简单细胞的响应调谐特性通过它们的前馈输入和在V1中看到的强递归的明显确定可以被整合到层2/3和4的相干电路模型中，在假设下，我们提供证据，递归作为抑制稳定的网络起作用：一种神经网络，其中兴奋性的重现足以引起不稳定性，但通过反馈抑制使电路稳定。我们将确定的条件下，该电路可以占经典和超经典的感受野特性和结构中观察到的自发活动，清楚地隔离的贡献的复发反应，并开发新的测试这种架构。(2)建立视觉皮层回路发育的生物学可识别和可测试的模型。特别是，研究的关键期（CP）单眼剥夺小鼠V1，我们将开发一个统一的模型的稳态和赫布CP可塑性，并从理论上测试的假设，即诱导CP的成熟抑制发生由于增加的比例，视觉活动的成熟所造成的自发活动。视觉皮层是我们用来看东西的大脑结构，它根据眼睛提供的信息创造我们的视觉感知。为了理解我们如何正常地看东西，以及斜视和弱视等中枢视觉障碍是如何产生和治疗的，理解视觉皮层的电路如何处理视觉信息并由视觉经验组织起来是至关重要的。这就是我们的研究目标。

Description (provided by applicant): We seek to understand the circuitry of visual cortex, the rules underlying its activity-dependent development, and the computational functions these subserve. These understandings are critical to our understanding both of normal vision and of its central disorders including amblyopia and strabismus. We focus on V1 as a model system. We use modeling to test coherent hypotheses as to the circuitry underlying V1 functional response properties and the plasticity rules underlying circuit development. Modeling allows testing of an integrated picture of circuit structure and/or developmental rules against a variety of experimental results and the development of new and unanticipated tests of that picture. The specific aims of this project are: (1) To create biologically identifiable and testable models of the mature circuitry of visual cortex. In particular, we will test the hypotheses (i) That intracellular as well as extracellular classical RF responses in LGN-recipient V1 simple cells, including a contrast-dependent decrease in voltage noise that is critical to contrast-invariant orientation tuning, can be quantitatively understood from simple, essentially feedforward models. (ii) That the apparent determination of the response tuning properties of LGN-recipient V1 simple cells by their feedforward input and the strong recurrence seen in V1 can be integrated into a coherent circuit model of layers 2/3 and 4 under the hypothesis, for which we provide evidence, that the recurrence functions as an inhibition-stabilized network: a network in which excitatory recurrence alone is strong enough to cause instability, but the circuit is stabilized by feedback inhibition. We will determine the conditions under which this circuit can account for classical and extra-classical receptive field properties and the structure observed in spontaneous activity, clearly isolate the contribution of the recurrence to responses, and develop novel tests of this architecture. (2) To create biologically identifiable and testable models of the development of the circuitry of visual cortex. In particular, studying the critical period (CP) for monocular deprivation in mouse V1, we will develop a unified model of homeostatic and Hebbian CP plasticity, and theoretically test the hypothesis that the induction of the CP by maturation of inhibition occurs due to an increase in the ratio of visual activity to spontaneous activity caused by that maturation. PUBLIC HEALTH RELEVANCE The visual cortex is the brain structure with which we see, creating our visual perception from the information provided by the eyes. To understand both how we see normally and how central visual disorders such as strabismus and amblyopia arise and can be treated, it is critical to understand how the circuitry of visual cortex processes visual information and is organized by visual experience. These are our research aims.