Functional Divergence at the Mouse Type 6 Bipolar Cell Terminal

鼠标 6 型双极电池端子的功能差异

基本信息

批准号：
9760822
负责人：
David Isaiah Swygart
金额：
$ 4.5万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9760822
关键词：
Amacrine Cells Anatomy Area Automobile Driving Behavioral Calcium Calcium Signaling Cells Closure by clamp Data Dendrites Development Electron Microscopy Glutamates Goals Image Individual Inner Plexiform Layer Link Location Mammalian Cell Measures Modeling Molecular Morphology Motion Mus Names Nervous system structure Neurites Neurons Noise Output Pathway interactions Pattern Pharmacology Photic Stimulation Physiological Presynaptic Terminals Property Research Retina Retinal Retinal Ganglion Cells Sensory Side Signal Transduction Specificity Stimulus Structure Synapses Testing Vision Visual Visual system structure Work cell type confocal imaging experimental study flexibility next generation parallel processing postsynaptic presynaptic receptive field receptor retinal prosthesis simulation two-photon visual information visual process visual processing voltage clamp

项目摘要

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.

项目概要在视觉系统的最早阶段，信号分为不同的通道，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约 40 个视网膜神经节传递视觉信号细胞类型。传统上，每种神经元类型都被认为传递单一信息通道。然而，这这一观点受到了非哺乳动物视网膜双极细胞能够执行亚细胞功能的证据的挑战。计算，使它们能够从同一小区的不同终端发送不同的信号。功能性在小型、电性相对紧凑的双极型器件中，尚未显示出突触水平的分歧。哺乳动物视网膜细胞。我的初步数据表明，同一类型 6 双极的不同端子细胞可以将不同的功能信号传递到小鼠的两种不同的视网膜神经节细胞类型上。我用共聚焦成像显示 6 型双极细胞和两种不同视网膜之间的解剖连接神经节细胞（ON alpha 和 PixON RGC）。提供 ON alpha 和 PixON RGC 均接收到的证据来自同一双极细胞的功能输入，我表明这些细胞具有高度的生理互相关性噪音。使用电压钳记录和视觉刺激，我表明 6 型双极电池提供激发对 ON α RGC 的环绕抑制非常小，但提供了显着的激发 PixON RGC 的环绕声抑制。此外，我展示了使用动态钳记录和模拟记录的电导表明，激励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。探索该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 GABA 能尖峰无长突细胞的突触前抑制，该细胞对 6 型双相情感障碍具有选择性为 PixON RGC 提供输入的端子。为了进一步研究无长突细胞的解剖结构这些终端，我将使用串行电子显微镜。最后，由于谷氨酸从双极电池末端释放是钙依赖性的，我将对来自 6 型双极端子的钙信号进行成像，以直接观察发散类型 6 端子处的信号。这些发现和提出的实验表明，每个终端单个双极细胞可能携带独特的视觉信号。这扩大了视觉通道的数量内部视网膜允许在视觉处理的最早阶段增加并行性。