Modulation of sensory hair cells by dopamine

多巴胺对感觉毛细胞的调节

基本信息

批准号：
8716170
负责人：
Cecilia Phillips Toro
金额：
$ 1.91万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8716170
关键词：
Afferent Neurons Antibodies Auditory Auditory system Behavioral Brain Calcium Channel Cell Count Cells Characteristics Cilia Circadian Rhythms Confocal Microscopy Data Dopamine Dopamine Agonists Dopamine D1 Receptor Dopamine Receptor Ear Efferent Neurons Electrophysiology (science)Endolymph Environment Esthesia Feedback Fertility Fishes Fluorescence Functional disorder Genetic Grant Hair Hair Cells Hearing Homeostasis Hour Hypothalamic structure Image Ion Channel Island Labyrinth Lead Lighting Location Mediating Microscopy Modeling Monitor Movement Nerve Neuraxis Neurons Neurotransmitters Organ Paralysed Pattern Perception Physiological Post-Traumatic Stress Disorders Receptor Activation Reflex action Role Schizophrenia Sensory Sensory Hair Sleep Staining method Stains Stereocilium Structure Synapses Techniques Testing Time Training Transgenic Organisms Translations Water Zebrafish auditory stimulus base cell type design dopaminergic neuron extracellular fluorophore in vivo imaging lateral line mutant nerve supply neuromast neurotransmitter release paracrine postsynaptic presynaptic public health relevance receptor research study sensor sensory stimulus sound transmission process voltage

项目摘要

DESCRIPTION (provided by applicant): The perception of vestibulo-auditory stimuli is controlled by both ascending afferent neurons from primary sensory organs, and descending modulatory efferent neurons from the brain. For over two decades we have known that efferents that release dopamine (DA) innervate vestibulo-auditory organs, yet the influence of DA on the primary mechanosensory cells-hair cells-is poorly understood. Zebrafish have many technical characteristics that make them uniquely suited to study neuronal circuits, including genetic tractability, high fecundity, transparency, low cell number, and superficial hair cells which all support excellent in vivo imaging and electrophysiology. I will use the zebrafish posterior lateral line (pLL) organ as a model for vertebrate vestibulo-auditory systems to understand the dopaminergic efferent circuit. The pLL is composed of neuromasts: islands of only ~12 hair cells that sense hydrodynamics, analogous to cells of the inner ear that are activated by movement of endolymph. Dopaminergic neurons that innervate the ear and pLL of zebrafish originate in the hypothalamus, an organ that regulates homeostasis, sleep, and circadian rhythms. The experiments in this proposal are designed to elucidate how DA modulates hair cells. Based on preliminary data, I hypothesize that the hypothalamus modulates the sensitivity of zebrafish to vestibulo-auditory stimuli by activating excitatory DA receptors expressed by hair cells. Results from these experiments will substantially contribute to our understanding of how the central nervous system can control perception of sensory stimuli by directly modulating primary sensory cells.

描述（由申请人提供）：前庭刺激的感知受主要感觉器官的升级传入神经元的控制，以及来自大脑的调节性传出神经元下降。二十年来，我们已经知道释放多巴胺（DA）支配前庭的受体器官的侵蚀者，但DA对主要的机械感力细胞毛细胞的影响 - 理解不足。斑马鱼具有许多技术特征，使它们非常适合研究神经元电路，包括遗传性障碍性，高繁殖力，透明度，低细胞数和表面毛细胞，这些细胞都支持体内成像和电生理学的出色。我将使用斑马鱼后侧面线（PLL）器官作为脊椎动物前庭原理系统的模型，以了解多巴胺能传出电路。 PLL由神经瘤组成：仅12个感知流体动力学的岛岛，类似于内耳的细胞，这些细胞被内淋巴运动激活。支配斑马鱼的耳朵和PLL的多巴胺能神经元起源于下丘脑，它是一种调节体内平衡，睡眠和昼夜节律的器官。该提案中的实验旨在阐明DA如何调节毛细胞。基于初步数据，我假设下丘脑通过激活毛细胞表达的兴奋性DA受体来调节斑马鱼对斑马鱼对冠状动物的刺激的敏感性。这些实验的结果将极大地有助于我们理解中枢神经系统如何通过直接调节原代感觉细胞来控制对感觉刺激的感知。