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Monitoring Real-Time Neuropeptide Dynamics

监测实时神经肽动态

基本信息

批准号：
10225612
负责人：
LESLIE A SOMBERS
金额：
$ 37.89万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10225612
关键词：
Adrenal Glands Amino Acids Behavior Biological Biological Models Brain Catecholamines Chemical Stimulation Chemicals Chromaffin Cells Collaborations Communities Complex Corpus striatum structure Data Decision Making Detection Development Diffusion Discrimination Disease Dopamine Drug Addiction Electrochemistry Electrodes Endocrine Engineering Enkephalins Extracellular Space Frequencies Goals Health In Situ Individual Knowledge Mass Spectrum Analysis Mediating Mediator of activation protein Membrane Methodology Methods Microdialysis Microelectrodes Mission Monitor Motivation Nafion Nature Neuropeptides Neurotransmitters Opioid Opioid Peptide Peptide Hydrolases Peptide Signal Sequences Peptides Periodicity Pharmacology Pharmacotherapy Physiologic pulse Physiological Physiological Processes Play Public Health Rattus Research Resolution Rewards Role Sampling Scanning Signal Transduction Slice Substance abuse problem Surface System Systems Development Time Tissues United States National Institutes of Health addiction brain tissue burden of illness carbon fiber cost design detection method double walled carbon nanotube drug of abuse drug reinforcement endogenous opioids evidence base experimental study extracellular hedonic improved in vivo individual response innovation insight motivated behavior nanoscale neurotransmission novel optogenetics rapid detection real time monitoring response reward processing sensor sensor technology small molecule stressor temporal measurement therapeutic target tool

项目摘要

ABSTRACT: The role of mesolimbic opioid peptides in motivated behavior and reward-related decision making is unclear, despite extensive evidence indicating that these molecules are important mediators of hedonic and motivational aspects of reward processing, and the fundamental response to drugs of abuse. This is largely due to a critical gap in understanding when and where these molecules are released, because there is a paucity of detection methods for monitoring opioid peptides in the extracellular space. We have established the feasibility of using fast-scan cyclic voltammetry (FSCV) and carbon- fiber microelectrodes in tissue for the detection of endogenous enkephalin (ENK) fluctuations in real time. The objective of this proposal is to optimize and fully characterize this methodology, so as to provide the community with an established tool that can be used to study the role of the ENKs in complex physiological processes ranging from basic endocrine function to motivation. The first goal is to fully characterize selectivity. We will assess incorporation of well-characterized Nafion composite membranes into the sensor design as a physical means to enhance selective detection. We will also investigate the electrochemistry of each of 20 natural amino acids individually, and use these data in a multivariate approach to identify individual amino acid contributors to the voltammetric signal when these residues are incorporated into longer amino acid chains. The second goal is to optimize sensitivity by systematically investigating electrochemical parameters (scan rates, holding potentials, and sampling frequencies), as well as promising nanoscale electrode materials. Finally, the third goal is to evaluate real-time ENK dynamics in rat adrenal and brain tissue, so as to provide insight into the normal concentration range, extracellular lifetime, and diffusion profile (sphere of influence) of the ENKs, as well as physiological and pharmacological conditions that can induce changes in peptidergic signaling. We will also directly compare the stimulation-response relationship for small molecule transmitters and ENK, using FSCV. This project is a critical step toward our long-term goal of elucidating how the release and clearance dynamics of several neuropeptides and small molecules underlie discrete aspects of motivated behavior. It will clarify outstanding questions regarding the fundamental nature of endogenous opioid peptide signaling, and enable FSCV to be used confidently to reveal critical mechanistic details that will inform evidence-based pharmacotherapies for treating a wide range of disorders, including substance abuse disorders.

文摘:

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Carbon-Fiber Nanoelectrodes for Real-Time Discrimination of Vesicle Cargo in the Native Cellular Environment.

DOI：
10.1021/acsnano.9b07318
发表时间：
2020-02
期刊：
ACS nano
影响因子：
17.1
作者：
James G. Roberts;Edwin C Mitchell;Lars E. Dunaway;G. McCarty;Leslie A. Sombers
通讯作者：
James G. Roberts;Edwin C Mitchell;Lars E. Dunaway;G. McCarty;Leslie A. Sombers

Neurotransmitter Readily Escapes Detection at the Opposing Microelectrode Surface in Typical Amperometric Measurements of Exocytosis at Single Cells.