Spatial mapping of receptor distributions on single identified neurons

单个已识别神经元上受体分布的空间映射

基本信息

批准号：
9049747
负责人：
Adriane Gerndt Otopalik
金额：
$ 2.88万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-16 至 2017-09-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9049747
关键词：
Address Amines Amino Acids Beds Behavioral Brain Cells Chemical Dynamics Chemicals Complement Complex Crustacea Custom Diffuse Disease Dopamine Exhibits Functional disorder GABA Receptor Ganglia Glutamate Receptor Glutamates Hormones Individual Lead Ligands Maps Measures Mediating Membrane Mental disorders Messenger RNA Morphology Motor Nervous system structure Neurites Neuromodulator Neurons Neuropeptides Neurotransmitters Optics Output Physiological Physiology Property Publishing Regulation Relative (related person)Signal Transduction Signaling Molecule Spatial Distribution Stereotyping Structure Synapses System Testing Transcript Transcriptional Regulation Weight Work cell type effective therapy electrical property flexibility gamma-Aminobutyric Acid ganglion cell mRNA Expression nervous system disorder neuronal circuitry neuroregulation public health relevance receptor receptor sensitivity response

项目摘要

DESCRIPTION (provided by applicant): The brain is subject to the action of numerous amino acids, amines, and neuropeptides. These local neurotransmitters and diffuse neuromodulators functionally reconfigure neuronal circuitry and allow for flexible, yet stable, behavioral output (Marder, 2012). Dysfunction of modulatory and transmitter systems has been implicated in a number of psychiatric and neurological disorders. In order to understand how the healthy brain mediates this dynamic chemical milieu, we must first understand how single neurons mediate the action of many signaling molecules. The proposed work addresses this question in the crustacean stomatogastric ganglion (STG), a small motor circuit containing 26-30 large, identifiable neurons with complex morphologies. All STG neurons are responsive to both GABA (Swensen et al., 2000) and glutamate (Marder & Paupardin- Tritsch, 1978; Cleland & Selverston, 1998). The subcellular distribution of GABA and glutamate ionotropic receptors, and the electrical properties of the compartments in which they function, likely dictates the weights with which these ligands influence the firing properties of single STG neurons. It is plausible tha these neurons differentially co-regulate and exhibit stereotyped spatial distributions of ionotropi receptors, and that these receptor distributions contribute to their unique firing properties. This hypothesis will be addressed using a custom optical system for focal photo-activation and mapping of ionotropic GABA and glutamate responses across the structures of different STG neuron types. These maps will be complemented with mRNA expression studies to determine if sensitivities to these two ligands are co-regulated in a compartment-specific or neuron- wide manner. Lastly, these maps will be used as a framework for understanding the functional relevance of subcellular receptor distributions in the face of a modulatory perturbation. Previous work has shown that dopamine alters glutamate receptor sensitivity in STG neurons (Cleland & Selverston, 1997; Johnson & Harris- Warrick, 1997). Focal photo-activation of glutamate receptors in tandem with spatially and temporally controlled iontophoretic dopamine administration will be used to probe whether this modulatory change in glutamate sensitivity occurs by uniformly or heterogeneously modulating different subcellular glutamate receptor loci across the structure of single neurons.

描述（由申请人提供）：大脑受到多种氨基酸、胺和神经肽的作用，这些局部神经递质和扩散神经调节剂在功能上重新配置神经元回路并允许灵活而稳定的行为输出（Marder，2012）。调节和传导系统的功能障碍与许多精神和神经疾病有关。为了了解健康的大脑如何介导这种动态的化学环境。必须首先了解单个神经元如何介导许多信号分子的作用，这项工作解决了甲壳类口胃神经节 (STG) 中的这个问题，这是一个包含 26-30 个具有复杂形态的大型可识别神经元的小型运动回路。 GABA（Swensen 等，2000）和谷氨酸（Marder & Paupardin-Tritsch，1978；Cleland & Selverston， 1998)。GABA 和谷氨酸离子型受体的亚细胞分布，以及它们发挥作用的区室的电特性，可能决定了这些配体影响单个 STG 神经元放电特性的权重，这些神经元的不同协同作用是合理的。 -调节并展示离子型受体的定型空间分布，并且这些受体分布有助于其独特的发射特性。该假设将使用定制光学系统进行焦点光激活，并绘制不同 STG 神经元类型结构中的离子型 GABA 和谷氨酸反应图谱。这些图谱将与 mRNA 表达研究相补充，以确定对这两种配体的敏感性是否一致。最后，这些图谱将用作理解亚细胞受体分布在调节扰动时的功能相关性的框架。多巴胺改变 STG 神经元中谷氨酸受体的敏感性（Cleland & Selverston，1997；Johnson & Harris-Warrick，1997）。谷氨酸受体的局部光激活与空间和时间控制的离子电渗多巴胺给药相结合将用于探测这种调节变化是否存在。谷氨酸敏感性是通过均匀或异质地调节单个细胞结构中不同的亚细胞谷氨酸受体基因座而发生的。神经元。