Retinal circuitry for precise coding

描述（由申请人提供）：我们拟研究视网膜回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生存的重要任务，如区分逃跑的动物和接近的动物，将是很重要的。视网膜向视觉世界发出信号的能力受到生物机制的限制，因为视网膜向大脑的输出受到饱和度和噪声的限制。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，这些机制的不可避免的代价是在信号中增加突触噪声，从而限制了细节的可见性。虽然我们对突触前到神经节细胞的回路了解很多，但除了重要的细节之外，我们还缺乏对其信号处理机制背后的基本原理的理解。例如，我们不知道神经节细胞的突触前回路是如何形成它的神经编码的，也不知道什么信号处理权衡是必要的，比如通过汇聚和间隙连接耦合将感受野中心信号池化，以及感受野周围从突起和水平细胞反馈中减法。利用表征神经节细胞和水平细胞的体外实时记录以及它们的现实计算模型，我们提出测试关于神经节细胞突触前回路在其敏感性和神经密码中的作用的几个假设。我们假设神经节细胞可以同时区分不同对比度、大小或位置的刺激，因为这些刺激是由不同的神经编码传递的。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，它在与行为相关的任务中使用对一对刺激的反应之间的似然规则进行区分，以测量神经元信号（例如对比或运动）的精度，并测量神经代码。利用理想的观察者分析来自视网膜神经元的单个和多个记录，我们将确定识别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节维持的突触释放率和接受野中心的信噪比（SNR），而这些也被周围环境调节。使用现场录音和模型，我们将研究神经节细胞的中心和环绕突触前电路如何控制其信噪比。最后，我们假设星爆腺分泌细胞之间的相互抑制产生正反馈以放大定向选择神经节细胞的定向信号。通过实时记录和模型，我们将验证互反突触反馈有助于星爆无突网络最大化运动方向的敏感性，并减少方向选择性神经节细胞中的噪声的假设。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，对大脑的基本理解，其行为和疾病的临床测试。

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.