STRUCTURE AND FUNCTION OF PARALLEL CHANNELS IN THE FOVEA

描述(由申请者提供)：我们的广泛目标是研究灵长类视网膜将大量信息传输到大脑的关键“设计”原则。它的106个轴突具有惊人的异质性。它们由15个通道组成，横跨轴突直径的50倍范围和尖峰频率的10倍范围。注意到中心凹回路受到空间和能量的强烈限制，我们假设存在多个通道，以便传递至少在“线体积”和新陈代谢能量方面的信息。初步研究表明，以低信息速率(几个比特/秒)传输的信道更有效(更多比特/尖峰)，并且物理上更小，因此使用更少的空间，并且可能更少的每比特能量。因此，以不同的速率获取信息的中央核(例如膝状M层与K层)至少可以接收到它们的信息。为了测试这一点，AIM 1将测量几种神经节细胞类型：(A)自然信息率(BITS/棘波和BITS/S对自然图像的反应)；(B)总导线体积(胞体+树突+轴突+终茎)(细胞密度)；(C)相对能量成本，即线粒体含量。我们预测，自然信息速率在不同频道之间差别很大，低速率频道每比特使用更少的空间和能量。 注意到非声道在空间上比在声道上更精细和密集，并且蓝色/黄色声道也在两个空间尺度上出现，我们假设接收视野大小和采样率被调整到自然场景中的信息分布。为了测试这一点，AIM 2将在与已知感受野相对应的尺度上测量自然图像中的非彩色和彩色信息。我们预测，在自然界中，暗区域占据的空间频率比明亮区域更高，每个视网膜区域包含的信息比明亮区域更多，因此需要更精细的通道和更多的突触；对于蓝色/黄色通道也有类似的预测。注意到通过视网膜的信息传输依赖于“带状”突触，我们假设它们以非常高的速度释放和收回囊泡。为了测试这一点，AIM 3将测量锥体突触的释放率(FM1-43染料的双光子+电子显微镜)，AIM 4将测量两极突触的释放率(电生理学+铁蛋白的EM)。 青光眼是导致失明的主要原因，神经节细胞缺氧和轴突运输减少都被认为是青光眼的主要原因。我们的研究将把神经节细胞信号与氧化能力和轴突运输能力联系起来，从而为未来的临床研究奠定基础。

DESCRIPTION (provided by applicant): Our broad goal is to investigate key 'design' principles by which the primate retina transfers large amounts of information to the brain. Its 106 axons are strikingly heterogeneous. They comprise 15 channels, spanning a 50-fold range in axon diameter and a 10-fold range in spike rate. Noting that foveal circuits are strongly constrained for space and energy, we hypothesize that multiple channels exist in order to relay information at least cost in "wire volume' and metabolic energy. Preliminary studies suggest that channels transmitting at low information rates (few bits/second) are more efficient (more bits/spike) and physically smaller, thus using less space and probably less energy per bit. Thus central nuclei, which acquire information at different rates (e.g. geniculate M vs. K layers), can receive their messages at least cost. To test this, AIM 1 will measure for several ganglion cell types: (a) 'natural information rate' (bits/spike and bits/s in response to natural images); (b) total wire volume (soma + dendrites + axon + terminal arbor)(cell density); (c) relative energy costs, i.e., mitochondrial content. We predict that natural information rates differ strongly across channels and that 'low-rate' channels use less space and energy per bit. Noting that OFF channels are spatially finer and denser than ON channels and that 'blue/yellow' channels also occur on two spatial scales, we hypothesize that receptive field sizes and sampling rates are tuned to the distribution of information in natural scenes. To test this, AIM 2 will measure achromatic and chromatic information in natural images on scales corresponding to known receptive fields. We predict that in nature dark regions occupy higher spatial frequencies and contain more information per retinal area than bright regions and thus require finer channels with more synapses; there are analogous predictions for the blue/yellow channels. Noting that information transfer through the retina relies on 'ribbon' synapses, we hypothesize that they release and retrieve vesicles at very high rates. To test this, AIM 3 will measure release rates at the cone synapse (2-photon + electron microscopy of FM1-43 dye), and AIM 4 will measure the rates at the bipolar synapse (electrophysiology + EM of ferritin). Glaucoma, a major cause of blindness, has been attributed to both ganglion cell anoxia and reduced axonal transport. Our studies will relate ganglion cell signaling to both oxidative capacity and axonal transport capacity, and thus should extend the basic foundation for future clinical studies.