Functional Divergence at the Mouse Type 6 Bipolar Cell Terminal

项目摘要 在视觉系统的最早阶段，信号分散到不同的通道，允许并行处理 的视觉信息。在小鼠视网膜中，13种视网膜双极细胞类型向~40个视网膜神经节传递视觉信号 细胞类型。传统上，每种神经元类型被认为传达单一的信息通道;然而， 非哺乳动物的视网膜双极细胞能够进行亚细胞功能， 计算，使它们能够从同一细胞的不同终端发送不同的信号。功能 在突触水平上的分歧尚未在小的、相对电紧凑的双极中示出。 哺乳动物视网膜的细胞。我的初步数据表明，同一类型6双极的不同终端 细胞可以将不同的功能信号传递到两种不同的视网膜神经节细胞类型。我用 共聚焦成像显示6型双极细胞和两个不同视网膜细胞之间的解剖连接 神经节细胞（ON alpha和PixON RGC）。为了提供ON alpha和PixON RGC都收到 功能输入从同一双极细胞，我表明，这些细胞具有较高的交叉相关性的生理 噪声使用电压钳记录和视觉刺激，我表明，6型双极细胞提供 对ON alpha RGC具有非常小的环绕抑制的激励，但是提供具有显著的环绕抑制的激励。 环绕声抑制到PixON RGC。此外，我使用动态钳记录和模拟 记录的电导表明，激励的周围抑制的差异是驱动差异的原因。 两个细胞的感受野特性。探讨这种功能的电路和细胞机制， 分歧，我使用受体和通道的药理学阻断来表明，6型双极细胞是 接受来自GABA能尖峰无长突细胞的突触前抑制，所述GABA能尖峰无长突细胞对那些6型双极细胞具有选择性， 为PixON RGC提供输入的端子。为了进一步研究无长突细胞的解剖， 这些终端，我将使用连续电子显微镜。最后，由于谷氨酸从双极细胞末端释放， 是钙依赖性的，我将成像钙信号从6型双极终端直接观察分歧 在6型终端的信号。这些发现和拟议的实验表明， 单个双极细胞可能携带独特视觉信号。这扩大了视觉通道的数量， 内层视网膜在视觉处理的最早阶段允许增加平行性。

Project Summary At the earliest stages of the visual system, signals diverge into separate channels, allowing for parallel processing of visual information. In the mouse retina, 13 retinal bipolar cell types convey visual signals to ~40 retinal ganglion cell types. Traditionally, each neuronal type was thought to convey a single channel of information; however, this view has been challenged by evidence that retinal bipolar cells of nonmammals are able to perform subcellular computations, enabling them to send different signals from different terminals of the same cell. Functional divergence at the level of the synapse has not been shown in the small, relatively electrically compact bipolar cells of the mammalian retina. My preliminary data suggests that different terminals of the same type 6 bipolar cell can transmit different functional signals onto two different retinal ganglion cell types in the mouse. I use confocal imaging to show anatomical connectivity between the type 6 bipolar cell and two different retinal ganglion cells (ON alpha and PixON RGCs). To provide evidence that both the ON alpha and PixON RGCs receive functional input from the same bipolar cell, I show that these cells have high cross correlation of physiological noise. Using voltage clamp recordings and visual stimulation, I show that the type 6 bipolar cell provides excitation with very little surround suppression to ON alpha RGCs but provides excitation with substantial surround suppression to PixON RGCs. Furthermore, I show using dynamic clamp recordings and simulation of recorded conductances that the difference in surround suppression of excitation is what drives the difference in the receptive field properties of the two cells. To explore the circuit and cellular mechanism of this functional divergence, I use pharmacological blockade of receptors and channels to suggest that the type 6 bipolar cell is receiving presynaptic inhibition from a GABAergic spiking amacrine cell that is selective for those type 6 bipolar terminals that provide input to the PixON RGC. To further investigate the anatomy of amacrine cells present at these terminals, I will use serial electron microscopy. Finally, since glutamate release from bipolar cell terminals is calcium dependent, I will image calcium signals from the type 6 bipolar terminals to directly observe divergence of signals at the type 6 terminals. These findings and proposed experiments indicate that each terminal of a single bipolar cell could potentially carry a unique visual signal. This expands the number of visual channels in the inner retina allowing for increased parallelism at the earliest stages of visual processing.