Olfactory Glomeruli: Cellular and Network Mechanisms

嗅觉肾小球：细胞和网络机制

基本信息

批准号：
9088442
负责人：
Michael Thomas Shipley
金额：
$ 32.62万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9088442
关键词：
Address Axon Birds Catabolism Cells Code Corpus striatum structure Data Dendrites Enzymes Equilibrium FDA approved Feedback Frequencies Funding Gene Targeting Health In Vitro Injection of therapeutic agent Kinetics Knowledge M cell Measures Metabolism Midbrain structure Molecular Molecular Profiling Morphology Mus Neurons Odors Output Parkinson Disease Pathway interactions Patients Perception Play Prosencephalon Regulation Rewards Role Scanning Schizophrenia Sensory Shapes Signal Transduction Smell Perception Structure Synapses System Testing Tomatoes Tyrosine 3-Monooxygenase Virus Whole-Cell Recordings addiction base cell type extracellular feeding gamma-Aminobutyric Acid in vivo inhibitor/antagonist inhibitory neuron neurophysiology novel strategies olfactory bulb olfactory bulb glomeruli operation optogenetics parallel processing postsynaptic presynaptic research study response reuptake sensory gating sensory input signal processing transmission process

项目摘要

DESCRIPTION (provided by applicant): Glomerular circuits are important. They transform sensory input into output signals that impact all downstream olfactory networks. Inhibition is key to these transforms. Intraglomerular inhibition presynaptically regulates sensory synapses and provides feedback and feed forward inhibition that shapes the strength and temporal structure of M/TC responses to sensory signals. Less is known about interglomerular inhibition. Exciting new data show that short axon cells, which form the interglomerular circuit, co-release GABA and DA. These co-transmitters trigger a temporally biphasic inhibitory-excitatory response in external tufted cells, neurons critical to glomerular circuit function. They also generate strong, temporally asymmetric, direct inhibition of M/TCs such that early-activated glomeruli inhibit their later activated neighbors, leading to "The early bird gets the worm" hypothesis. These discoveries were made using optogenetics combined with recordings from identified gene-targeted cell-type specific neurons. Little is known about DA release or it's metabolism in the bulb. Fast Scan Cyclic Voltammetry will be used to define the kinetics of DA release in vitro and in vivo. New data suggest that FDA-approved COMT inhibitors may enhance bulb DA function; this could benefit Parkinson's patients. We will test this hypothesis. Inhibitory-inhibitory interactions among inter- and intraglomerular neurons have not been explored. Pilot data using optogenetics combined with identified cell recordings indicate robust interactions. We will define inhibitory-inhibitory interactions, their synaptic dynamics and how they shape intra- and interglomerular signaling.

描述（由申请人提供）：肾小球电路很重要。他们将感觉输入转换为影响所有下游嗅觉网络的输出信号。抑制是这些转换的关键。倾斜内抑制突触前调节感觉突触，并提供反馈和进食抑制作用，从而塑造了M/TC对感觉信号的强度和时间结构。关于胶体间抑制的了解少。令人兴奋的新数据表明，短轴突细胞形成了胶合间电路，共同发行的GABA和DA。这些co弹器在外部簇状细胞中引发了暂时的双相抑制作用反应，神经元对肾小球电路功能至关重要。它们还会产生强大的，时间不对称的直接抑制M/TC，使得早期激活的肾小球抑制它们后来激活的邻居，导致“早鸟得到蠕虫”假设。这些发现是使用光遗传学与鉴定出基因靶向细胞类型特异性神经元的记录相结合的。关于DA释放或灯泡中的代谢知之甚少。快速扫描循环伏安法将用于定义体外和体内DA释放的动力学。新数据表明，FDA批准的COMT抑制剂可能会增强灯泡DA功能。这可以使帕金森病人受益。我们将检验这一假设。尚未探索抑制性抑制性相互作用和磁内神经元之间的抑制性相互作用。使用光遗传学与已识别的细胞记录相结合的试点数据表明鲁棒的相互作用。我们将定义抑制性抑制性相互作用，它们的突触动力学以及它们如何塑造内部和盆腔间信号传导。