MECHANISMS FOR TEMPORAL CODING BY RETINAL GANGLION CELL

视网膜神经节细胞的时间编码机制

• 批准号: 6635723
• 负责人: MICHAEL A FREED
• 金额: $ 23.78万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635723
• 关键词: action potentials; amacrine cells; cats; electron microscopy; eye pharmacology; guinea pigs; information theory; membrane channels; neural information processing; neuroanatomy; neurophysiology; retinal bipolar neuron; retinal ganglion; stimulus /response; stimulus interval; synapses; visual stimulus

DESCRIPTION (Applicant's Description): When a visual stimulus is presented repeatedly, a ganglion cell fires spikes at nearly identical times, often within 1 ms. This remarkable precision may support a timing code, which compared to a rate code can carry more information per spike. Previous research used extracellular recording to characterize the temporal precision of the ganglion cell's spike output. I propose to use whole-cell and intracellular recordings to identify mechanisms (microcircuits and ion channels) that set the timing of the ganglion cell's synaptic inputs. This effort has three parts: (1) Identify mechanisms that cause precise timing of the ganglion cell's input. Preliminary studies show ganglion cells with sequences of spontaneous postsynaptic currents (PSC) whose times are strongly correlated, often within 2 ms. Thus, precise timing of synaptic input might contribute to precise timing at the spike output. I will determine the mechanism(s) responsible for setting the timing of PSC inputs and determine how altering these mechanisms affects PSC timing. For example, preliminary studies show that inhibiting L-type calcium currents decorrelates PSCs. (2) Test the hypothesis that distinct microcircuits cause distinct patterns of input timing. Ganglion cells exhibit various cross-correlation patterns between glutamatergic (bipolar) PSCs and autocorrelations between GABA/Glycinergic (amacrine) PSCs. I will identify these patterns for specific morphological types of ganglion cell. I will then examine their synaptic input with the electron microscope to determine which circuit features, such as feedforward or feedback synapses, correspond to different correlation patterns. (3) Determine how efficiently the ganglion cell encodes its input as a spike train output. This will be accomplished in the intact retina by intracellularly injecting random amplitude currents (simulated postsynaptic currents) and measuring the ganglion cell's intrinsic temporal precision and information coding capacity. Then, by stimulating with random light intensities, I will measure the actual rate of information transmission. To transmit information requires metabolic energy, thus there may be selective pressure to match the ganglion cell's intrinsic information capacity to the amount of information that it actually transmits. These studies will advance a basic understanding of how discrete neural events (vesicular synaptic release and spike generation) might implement a timing code in the mammalian retina.

描述（申请人的描述）：显示视觉刺激时 一再，一个神经节细胞在几乎相同的时间发射尖峰，通常 在1毫秒内。这个非凡的精度可能支持一个计时代码，该计时代码 与速率代码相比，每个峰值可以携带更多信息。先前的研究 使用细胞外记录来表征 神经节细胞的尖峰输出。我建议使用全细胞和细胞内 记录以识别设置的机制（微电路和离子通道） 神经节细胞的突触输入的时间。这项工作有三个部分：（1） 确定导致神经节细胞输入精确时机的机制。 初步研究表明，神经节细胞具有自发的序列 突触后电流（PSC）的时代密切相关，通常在2 多发性硬化症。因此，突触输入的精确时机可能有助于精确的时机 在尖峰输出。我将确定负责设置的机制 PSC输入的时间安排，并确定这些机制如何影响 PSC计时。例如，初步研究表明，抑制L型 钙电流解变PSC。 （2）检验以下假设 微电路会导致输入时序的不同模式。神经节细胞表现出 谷氨酸能（双极）PSC和 GABA/甘氨酸（氨基氨酸）PSC之间的自相关。我会识别的 这些模式用于神经节细胞的特定形态类型。然后我会 检查他们使用电子显微镜的突触输入，以确定哪个 电路功能（例如前馈或反馈突触）对应于 不同的相关模式。 （3）确定神经节细胞的有效程度 将其输入编码为尖峰火车输出。这将在 完整的视网膜通过细胞内注射随机振幅电流（模拟 突触后电流）并测量神经节细胞的固有时间 精度和信息编码能力。然后，通过随机刺激 光强度，我将衡量信息传输的实际速率。 传输信息需要代谢能量，因此可能有选择性 与神经节细胞的固有信息能力相匹配的压力 它实际传输的信息量。这些研究将推进 对离散神经事件的基本了解（囊泡突触释放 和Spike Generation）可能会在哺乳动物视网膜中实施计时代码。