Retinal circuitry for precise coding

描述（由申请人提供）：我们建议研究视网膜电路编码不同类型刺激特征的精度。这对于理解视网膜回路如何告知大脑对生存至关重要的任务（例如区分逃跑的动物和接近的动物）非常重要。视网膜向视觉世界发出信号的能力受到生物机制的限制，因为视网膜向大脑的输出受到饱和度和噪声的限制。为了科普这个问题，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精细细节。然而，这些机制的不可避免的代价是将突触噪声添加到信号中，这限制了精细细节的可见性。虽然我们对神经节细胞突触前的神经回路了解很多，但除了重要的细节之外，还缺乏对其信号处理机制背后的基本原理的理解。例如，神经节细胞的突触前回路如何形成其神经代码是未知的，可以告知刺激的响应模式，也不知道什么信号处理权衡使得需要这样的回路机制，如通过会聚和间隙连接耦合的感受野中心信号的汇集，以及从无长突和水平细胞反馈的感受野环绕减法。使用在体外的活记录，从其特点的神经节细胞和水平细胞和现实的计算模型，他们，我们建议测试几个假设的神经节细胞的敏感性和神经代码的突触前电路的作用。我们假设，神经节细胞可以同时区分几个不同的刺激，在对比度，大小或位置，因为这些刺激是由不同的神经代码传达。我们将用一个理想的观察者来分析神经反应，这是一个计算机程序，它使用行为相关任务中对一对刺激的反应之间的似然规则来区分，以测量神经元发出信号（例如对比度或运动）的精度，并测量神经代码。使用理想的观察者来分析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代码。接下来，我们假设中继背景水平的视网膜信号调节维持的突触释放速率和感受野中心的信噪比（SNR），并且这些也被周围环境调制。我们将使用现场录音和模型，研究神经节细胞的突触前中枢和周围神经回路如何控制其信噪比。最后，我们假设星状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。使用现场录音和模型，我们将测试的假设，相互突触反馈帮助星爆无长突网络最大限度地提高对运动方向的敏感性，并减少噪音的方向选择性神经节细胞。这些拟议的研究是新的和重要的，将提供有关电路功能的知识，以基本了解大脑，其行为和疾病的临床测试。 公共卫生相关性：视网膜回路的拟议研究将提供有关视网膜如何可靠地检测视觉环境特征的新知识。理想观察者分析的使用允许将一个或多个神经元的性能与一个人看相同刺激的性能进行比较。这种方法提供的结果与公共卫生有关，因为它将帮助科学家和眼科医生确定健康和疾病中负责视觉的神经回路。

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.