Retinal circuitry for precise coding

描述(由申请人提供)：我们建议研究视网膜回路编码不同类型的刺激特征的精确度。这对于理解视网膜回路如何向大脑告知对生存至关重要的任务非常重要，例如区分逃跑的动物和接近的动物，这将是重要的。视网膜向视觉世界发出信号的能力受到生物机制的限制，因为视网膜输出到大脑的能力受到饱和度和噪音的限制。为了解决这个问题，视网膜使用各种适应机制去除背景水平，允许神经节细胞信号编码细节。然而，这些机制不可避免的代价是信号中增加了突触噪声，这限制了细节的可见性。虽然对神经节细胞的突触前回路已知很多，但除了重要的细节外，缺乏的是对其信号处理机制背后的原理的理解。例如，尚不清楚神经节细胞的突触前电路是如何形成其神经代码的，也不知道可以告知刺激的反应模式，也不知道是什么信号处理权衡了必要的电路机制，如通过会聚和缝隙连接耦合汇集感受野中心信号，以及感受野周围从无长突细胞和水平细胞反馈中减去。利用特征化的神经节细胞和水平细胞的体外实时记录和它们的真实计算模型，我们提出了几个关于突触前回路在神经节细胞的敏感性和神经编码中所起作用的假设。我们假设神经节细胞可以同时区分不同对比度、大小或位置的几个刺激，因为这些刺激是由不同的神经编码传达的。我们将使用理想的观察者来分析神经反应，这是一个计算机程序，它使用似然规则在与行为相关的任务中区分对一对刺激的反应，以测量神经元发出信号(例如对比或运动)的精度，并测量神经代码。使用理想的观察者来分析来自视网膜神经元的单个和多个记录，我们将确定区分多个视觉特征的灵敏度和神经编码。接下来，我们假设，传递背景水平的视网膜信号调制了感受场中心维持的突触释放速率和信噪比(SNR)，并且这些也受到了周围环境的调制。利用现场录音和模型，我们将研究神经节细胞的中枢和周围突触前回路如何控制其信噪比。最后，我们假设星爆无长突细胞之间的相互抑制产生正反馈，以放大方向选择性神经节细胞的方向信号。利用现场录音和模型，我们将检验这一假说，即相互突触反馈帮助星爆无长突网络最大化对运动方向的敏感性，并减少方向选择性神经节细胞中的噪音。这些拟议的研究是新的和重要的，将提供与基本了解大脑、其行为和疾病的临床测试相关的电路功能的知识。 与公共健康相关：拟议中的视网膜电路研究将提供有关视网膜如何工作的新知识，以可靠地检测视觉环境的特征。理想观察者分析的使用允许将一个或几个神经元的性能与观察相同刺激的人的性能进行比较。这种方法提供的结果与公共健康相关，因为它将帮助科学家和眼科医生确定在健康和疾病中负责视力的神经回路。

DESCRIPTION (provided by applicant): We propose to study the precision with which retinal circuits code different types of stimulus features. This will be important for understanding how retinal circuits inform the brain about tasks important for survival such as distinguishing a fleeing animal from one approaching. The retina's ability to signal the visual world is limited by biological mechanisms, because the retinal output to the brain is limited by saturation and noise. To cope with this problem, the retina removes the background level using a variety of adaptation mechanisms, allowing ganglion cell signals to code for fine details. However the inevitable cost of these mechanisms is the addition of synaptic noise to the signal which limits fine details' visibility. Although much is known about circuits presynaptic to ganglion cells, what is lacking beyond important details is an understanding of the rationale behind their signal processing mechanisms. For example, it is unknown how a ganglion cell's presynaptic circuit shapes its neural code, the pattern of response that can inform about a stimulus, nor is it known what signal processing tradeoffs make necessary such circuit mechanisms as pooling of the receptive field center signal by convergence and gap junction coupling, and receptive field surround subtraction from amacrine and horizontal cell feedback. Using in vitro live recordings from characterized ganglion cells and horizontal cells and realistic computational models of them, we propose to test several hypotheses about the role of circuits presynaptic to the ganglion cell in its sensitivity and neural code. We hypothesize that a ganglion cell can simultaneously distinguish several stimuli that differ in contrast, size, or location, because these stimuli are conveyed by different neural codes. We will analyze the neural responses with an ideal observer, a computer program that discriminates using the likelihood rule between the responses to a pair of stimuli in a behaviorally-relevant task to measure the precision with which a neuron signals e.g. contrast or motion, and to measure the neural code. Using the ideal observer to analyze single and multiple recordings from retinal neurons, we will determine the sensitivity and neural code for discriminating multiple visual features. Next, we hypothesize that the retinal signal that relays the background level modulates the maintained synaptic release rate and signal-to-noise ratio (SNR) of the receptive field center, and that these are also modulated by the surround. Using live recordings and models, we will study how the ganglion cell's presynaptic circuitry for center and surround control its SNR. Last, we hypothesize that reciprocal inhibition between starburst amacrine cells generates positive feedback to amplify the directional signal for the direction-selective ganglion cell. Using live recordings and models, we will test the hypothesis that reciprocal synaptic feedback helps the starburst amacrine network maximize sensitivity to direction of motion and reduce noise in the direction- selective ganglion cell. These proposed studies are new and important and will provide knowledge about circuit function relevant to a basic understanding of the brain, its behavior, and clinical testing of disease. PUBLIC HEALTH RELEVANCE: The proposed studies of retinal circuitry will provide new knowledge about how the retina functions to reliably detect features of the visual environment. The use of ideal observer analysis allows comparing the performance of one or several neurons to the performance of a person looking at the same stimulus. The results provided by this method are relevant to public health because it will help scientists and eye doctors to determine the neural circuits that are responsible for vision in health and disease.