Models of visual cortical circuitry and development

描述(由申请人提供)：我们试图了解视觉皮质的回路，其依赖活动的发育的潜在规则，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疾病都是至关重要的。我们把V1作为一个模型系统来关注。我们使用建模来检验关于潜在的V1功能响应特性的电路的一致性假设和潜在的电路发展的可塑性规则。建模允许对照各种实验结果测试电路结构和/或发展规则的集成画面，并开发该画面的新的和未预料到的测试。这个项目的具体目标是：(1)建立生物上可识别和可测试的视皮层成熟回路模型。特别是，我们将测试假设(I)，即LGN受体V1简单细胞中的细胞内和细胞外的经典RF反应，包括对比度相关的电压噪声的减少，这对对比度不变的取向调节至关重要，可以从简单的、基本上是前馈的模型中定量地理解。(Ii)LGN受体V1简单细胞的反应调谐特性由其前馈输入和V1中所见的强重现的明显决定可以整合到2/3层和4层的相干电路模型中，我们为该假设提供了证据：在该网络中，仅兴奋性重现就足以引起不稳定，但该网络通过反馈抑制来稳定。我们将确定该电路能够解释经典和超经典感受场属性以及自发活动中观察到的结构的条件，清楚地分离重复对反应的贡献，并开发这种结构的新测试。(2)建立生物可识别和可测试的视皮层回路发育模型。特别是，在研究小鼠V1单眼剥夺的临界期(CP)时，我们将建立一个稳态和Hebbian CP可塑性的统一模型，并从理论上检验这样一种假设，即抑制成熟导致的CP的诱导是由于这种成熟引起的视觉活动与自发活动的比率增加。公共卫生相关性视觉皮质是我们用来看东西的大脑结构，通过眼睛提供的信息来创造我们的视觉感知。要了解我们如何正常观看，以及中枢性视觉障碍(如斜视和弱视)是如何发生和如何治疗的，关键是要了解视觉皮质的回路是如何处理视觉信息并由视觉经验组织起来的。这些都是我们的研究目标。

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.