Dendritic Integration and Direction Selectivity in Starburst Amacrine Cells

星爆无长突细胞中的树突整合和方向选择性

• 批准号: 8783056
• 负责人: Anna Vlasits
• 金额: $ 3.62万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8783056
• 关键词: Action Potentials; Alzheimer' s Disease; Amacrine Cells; Antibodies; Autistic Disorder; Back; Blindness; Brain; Calcium; Cell physiology; Cells; Dendrites; Disease; Distal; Dyes; Electrophysiology (science); Exhibits; Eye; Fire - disasters; Glutamate Receptor; Glutamates; Goals; Health; Human; Image; Imaging Techniques; Individual; Interneurons; Knowledge; Lead; Light; Link; Location; Maps; Measures; Mediating; Membrane; Membrane Potentials; Mental Retardation; Methods; Neural Retina; Neurons; Neurotransmitters; Paralysed; Pathology; Pattern; Pharmacology; Photic Stimulation; Physiological; Protocols documentation; Research; Retina; Retinal; Role; Sensory Disorders; Signal Transduction; Site; Source; Staining method; Stains; Stimulus; Structure; Synapses; Testing; Time; Tissues; Visual Motion; Work; cell type; deafness; design; gamma-Aminobutyric Acid; ganglion cell; neural prosthesis; neuronal cell body; neuropsychiatry; neurotransmitter release; public health relevance; research study; response; sensory system; voltage

DESCRIPTION (provided by applicant): In the retina, direction selective ganglion cells fire many action potentials in response to light stimuli moving in a preferred direction and few action potentials to light moving in the opposite direction. Asymmetric release of gamma-aminobutyric acid (GABA) from starburst amacrine cells dendrites is thought to confer this direction selective tuning to direction selective ganglion cells. Starburst amacrine cells have been shown to exhibit a larger increase in Ca2+ in their distal dendrites near GABA release sites during stimulation with light moving from their soma toward the distal dendrites compared with light moving from the distal dendrites toward the soma. The source and consequence of this asymmetry in Ca2+ levels are not well understood. In this proposal, I explore the hypothesis that starburst amacrine cells compute direction autonomously in individual dendrites. How a dendrite integrates its inputs is of broad importance because it is one of the key steps in neuronal signaling in all neurons with multiple inputs. Starburst amacrine cells are distinct from many other cell types because their integration point is located in the distal end of the dendrite rather than at the soma. In addition, in contrast to many other neuron types, the question of how the starburst amacrine cell integrates its inputs is relevant to the known physiological function of the cell sine the order of inputs is directly related to the direction of moving light stimuli. Therefore understanding integration in starburst cell dendrites will contribute directly to our understanding of the role of starburst amacrine cells in the retinal circuit. Using electrophysiology, glutamate uncaging and imaging techniques, I will determine whether an intrinsic non-linearity in the starburst cell dendrites favors bipolar cell inputs arriving sequentially from the soma toward the release sites in the distal dendrites over inputs arriving in the opposite order (Aim 1). In additin, I propose experiments to determine whether the previously observed increase in Ca2+ during stimulation toward distal dendrites leads to an increase in inhibition from starburst amacrine cells onto direction selective ganglion cells (Aim 2). Lastly, I propose experiments to determine the role of voltage-gated Ca2+ channels in establishing the asymmetry in Ca2+ influx and GABA release from starburst amacrine cell dendrites (Aim 3).

描述（由申请人提供）：在视网膜中，方向选择性神经节细胞响应于沿优选方向移动的光刺激而激发许多动作电位，而响应于沿相反方向移动的光刺激而激发很少的动作电位。星爆无长突细胞树突中不对称释放γ-氨基丁酸（GABA）被认为赋予方向选择性神经节细胞这种方向选择性调节。与从远端树突向体细胞移动的光相比，星爆无长突细胞在光从体体向远端树突移动的刺激过程中，其靠近 GABA 释放位点的远端树突中的 Ca2+ 表现出更大的增加。这种 Ca2+ 水平不对称的来源和后果尚不清楚。 在这个提案中，我探讨了星爆无长突的假设 细胞自主计算单个树突的方向。树突如何整合其输入具有广泛的重要性，因为它是具有多个输入的所有神经元中神经元信号传导的关键步骤之一。星爆型无长突细胞与许多其他细胞类型不同，因为它们的整合点位于树突的远端而不是胞体。此外，与许多其他神经元类型相比，星爆无长突细胞如何整合其输入的问题与细胞的已知生理功能相关，因为输入的顺序与移动光刺激的方向直接相关。因此，了解星爆细胞树突中的整合将直接有助于我们的理解 星爆无长突细胞在视网膜回路中的作用。 利用电生理学，谷氨酸 通过释放和成像技术，我将确定星爆细胞树突中的固有非线性是否有利于双极细胞输入从体细胞按顺序到达远端树突的释放位点，而不是以相反顺序到达的输入（目标1）。此外，我建议进行实验来确定先前观察到的在刺激远端树突期间 Ca2+ 的增加是否会导致星爆无长突细胞对方向选择性神经节细胞的抑制增加（目标 2）。最后，我提出实验来确定电压门控 Ca2+ 通道在建立星爆无长突细胞树突的 Ca2+ 流入和 GABA 释放不对称性中的作用（目标 3）。