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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.