Name: modeling fast-scan cyclic voltammetry data from electrically stimulated dopamine neurotransmission data using qnsim1.0
Uploaded: 2017-06-05T12:30:00
Description: Watch this Scientific Journal Video about Modeling Fast-scan Cyclic Voltammetry Data from Electrically Stimulated Dopamine Neurotransmission Data Using QNsim1.0 at JoVE.com

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1.安装，数据准备和启动QNsim1.0 <ol><li>下载“QNsim1.0.zip”（作为补充提供），并将其解压缩到所需的目录。 </li><li>通过组织电子表格准备刺激的DA响应数据，用于通过软件程序进行建模，其中每列包含转换为μM DA浓度的时间DA响应。将此（.xlsx）文件另存为与程序文件相同的目录。 注意：电子表格可以包含单个实验中的多个响应或包含固定数量响应的多个研究（有关示例，请参阅“Sample.xlsx?...

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A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determination+of+release+and+uptake+parameters+from+electrically+evoked+dopamine+dynamics+measured+by+real-time+voltammetry.">Determination of release and uptake parameters from electrically evoked dopamine dynamics measured by real-time voltammetry.</a> J Neurosci Methods. 112 (2), 119-133 (2001).</li></ol>

使用FSCV研究体内刺激的DA神经传递起源于20世纪80年代30 ，仍然是具有无与伦比的空间和时间分辨率的体内神经传递数据的丰富来源。受刺激的DA响应反映了由电刺激本身调制的DA释放和再摄取的复杂平衡。 QN模型结合了来自当代神经传递研究的原理，在动态释放和再摄取假设方面对体内刺激的DA神经传递数据进行建模。此外，QN框架将可能的FSCV分析范围...

多巴胺（DA）神经传递在各种认知和行为功能中起重要作用，其功能障碍涉及几种常见的疾病和障碍。因此，开发定量研究体内 DA神经传递的准确方法至关重要，以评估DA神经传递在疾病模型和药物药理学背景下的变化。快速扫描循环伏安法（FSCV）允许在体内 DA神经传递监测，具有良好的空间和时间分辨率。虽然可以监测生理DA神经传递在清醒，自由行动的动物，麻醉动物的上升多巴胺能途径的电刺激可以产生稳定的DA反应，适合DA神经传递的增强的动力学分析。 电刺激的DA响应反映了DA释放和再摄取以及解释的动态相互作用这些反应主要使用被称为Michaelis-Menten（MM）模型12的刺激DA神经传递的简单模型。 MM模型由3个变量组成，根据恒定的DA释放速率和恒定的再摄取效率（ 即， DA再摄取速率和细胞外DA浓度之间的关系）来描述DA响应，如等式1所述 ： <img alt="公式1" src="/files/ftp_upload/55595/55595eq1.jpg" /> （DA释放）（DA再摄取） 在等式1中， f是刺激的频率; [DA] p是每脉冲刺激的估计的DA浓度增加; V max表示估计的最大再摄取速率;并且K m是估计的MM常数，其在理论上等同于饱和DAT的50％的细胞外DA浓度，导致半最大再摄取速率。这个差异可以通过估计[DA] p ，V max和K m参数来整合等式来模拟实验DA响应。 虽然MM模型有助于在各种实验环境中了解DA神经传递动力学方面的显着进步，但MM模型制作了简单的基本假设，限制了其在超生理刺激引起的DA反应建模时的适用性。例如，如果MM模型以凸起方式上升，则MM模型只能近似DA响应形状，但不能解释在背纹纹区域12中发现的渐进（凹）上升响应。因此，MM模型假设不能准确地捕获受激DA神经传递的动态释放和再摄取过程。 根据现实的量子来模拟受激DA响应基于互补研究和实验的刺激神经传递动力学原理，开发了定量神经生物学（QN）框架。各种神经传递研究表明，（1）刺激的神经递质释放是在刺激过程中速率降低的动态过程14 ，（2）在双相衰变动力学15后的刺激后期释放继续发生，和（3）DA在刺激持续时间2,16期间，再摄取效率逐渐被抑制。这三个概念作为QN框架的基础，三个方程由描述DA释放和再摄取动力学的12个参数组成（ 表1 ）。 QN框架可以密切模拟异质实验DA响应类型，以及p刺激参数和药物给药的实验操作的改变效果2,6 。虽然进一步的研究是必要的，以完善数据建模方法，未来的实验可以极大地受益于这种神经生物学接地的建模方法，这显着增加了从受刺激的DA神经传递范式中得出的推论。 <img alt="表格1" src="/files/ftp_upload/55595/55595tbl1.jpg" /> 表1： 建模方程和参数 。 <a href="http://ecsource.jove.com/files/ftp_upload/55595/55595tbl1large.jpg" target="_blank">请点击此处查看此图的较大版本。</a> 本教程介绍如何使用QNsim 1.0对受激DA响应数据进行建模以估计DA释放和再摄取动力学。实际实验数据收集这里不描述加工，并且仅需要时间DA浓度数据。 QN框架的理论支持和基础已经在前面已经有很多的描述2 ，但是对应用QN框架来建立DA响应数据的实际观点如下所述。 QN框架模拟动态相互作用：1）动态DA释放，2）DA再摄取; 3）超生理刺激对这些过程的影响，从DA响应数据中提取有意义的动力学信息。 QN框架最适合于使用高持续时间（ 例如， 60 Hz，10 s刺激）的高度超生理刺激获取的FSCV数据，其产生适用于动力学分析的强大的DA响应。在对底层释放和再摄取过程进行准确建模之后，可以使用模型参数来模拟DA反应，其应近似于ex感应DA响应。 QN框架的方程式描述了在受刺激的DA反应过程中DA释放和再摄取的速率。当刺激的DA释放速率在刺激过程中指数下降时，QN框架描述了刺激的DA释放速率作为从刺激开始（t 刺激 ）开始的时间的函数。这与容易释放的池的耗尽一致，具有补充的稳态DA释放速率（DARss）以解释囊泡补充，类似于其他报告（ 等式2 ） 14,17 。 <img alt="公式2" src="/files/ftp_upload/55595/55595eq2.jpg" />增加DA释放速率的操作，例如增加ΔDAR，ΔDARτ或DARss导致DA与时间图的响应幅度增加。每个参数ter对DA响应形状有差异。增加DARss和ΔDARτ都使得响应的上升阶段更线性（较少凸）。降低ΔDARτ促进凸度，其由ΔDAR的大小控制。基于建模经验，DARss通常小于ΔDAR的1/5;因此，ΔDAR是主要确定DA响应的总体响应幅度的释放参数。 刺激后DA释放速率由等式3建模为刺激结束时刺激的DA释放速率（DAR ES ）的延续，作为刺激后（t post ）时间的函数。后刺激DA释放速率遵循双相衰变模式，如前所述15 ，具有快速指数衰减期和延长的线性衰变期以模拟两个ca依赖于依赖的神经递质释放过程。 <img alt="公式4" src="/files/ftp_upload/55595/55595eq4.jpg" /> （快速指数衰减）（长时间线性衰减） 目前不可能确定发生多少刺激后DA释放。可以通过系统地最小化刺激后DA释放的估计和跨越从使用不同刺激持续时间的同一记录位点收集的一组实验DA响应来验证模型参数来解决这个限制。这种最小化允许用户对释放和再摄取进行保守的估计。因为电刺激导致促进刺激后神经递质释放的钙积聚，刺激的持续时间影响后刺激神经元垃圾释放参数18,19 。基于建模经验，发现随着刺激持续时间的增加，τR增加，X R降低，与更大的钙积累的预期效果相一致20 。 方程4描述了作为MM框架的扩展的DA再摄取速率并且包含动态K m项，其在刺激期间增加以模拟由超生理刺激2,16引起的逐渐降低的再摄取效率。刺激结束后K m保持恒定在K m值（K mES ）。 <img alt="公式5" src="/files/ftp_upload/55595/55595eq5.jpg" />哪里， <img alt =“等式6”src =“/ files / ftp_upload / 55595 / 55595eq6.jpg”/&gt; （刺激期间）（刺激后） 刺激的DA反应，特别是从腹侧纹状体区域，往往对初始K m值（K mi ）的变化不敏感，这使得定义K mi值有问题。因此，像原始的MM框架一样，从对照未处理的动物12收集的DA反应，K mi近似为0.1-0.4μM。 ΔK m项决定了刺激过程中再摄取效率变化的程度，从我们的经验来看，约为2081; M在60Hz，10s刺激过程中。 k和K minf值确定K m随着时间的推移而改变，并且增加这些项中的任一个可以促进上升阶段的凹陷。 V max是部分与局部DA转运体密度相关的最大再摄取速率，其表现出腹外侧至背侧梯度21 。因此，背侧纹状体（D-Str）中的V max值通常大于30μM / s，但通常在腹侧区域（如伏核（NAc） 6 ））小于30μM / s。 上述一般准则可以帮助建模实验DA响应数据，但是生成近似实验DA响应的仿真需要迭代地调整模型参数。可以通过获得提供的超生理刺激的DA响应来改善模型参数的准确性一个强大的基板用于模拟，以及通过获得和建模多个DA响应来刺激在相同记录位置（ 例如， 60Hz，5s和10s的刺激）的不同持续时间以验证参数的准确性（参见样本数据）。为了证明，在已经使用QN框架建模的药理学挑战之前和之后，在包含在伏隔核和背纹纹状体中收集的区域特异性刺激的DA应答的软件包中包含数据集。通过扩展，用户将发现这种方法可以类似地应用于表征DA神经传递在各种疾病背景和药理学操作中的动力学。

<table border="0" cellpadding="0" cellspacing="0" width="750">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">MATLAB R2016a for Mac&#160;</td>
			<td style="width:99px;">Mathworks</td>
			<td style="width:119px;"></td>
			<td style="width:317px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">QNsim1.0</td>
			<td style="width:99px;">In house software package</td>
			<td style="width:119px;"></td>
			<td>Software to model FSCV data using the QN framework</td>
		</tr>
	</tbody>
</table>

modeling fast-scan cyclic voltammetry data from electrically stimulated dopamine neurotransmission data using qnsim1.0

中枢多巴胺能（DAergic）途径在广泛的功能（如注意力，动机和运动）中具有重要作用。多巴胺（DA）涉及疾病和病症，包括注意缺陷多动障碍，帕金森病和创伤性脑损伤。因此，DA神经传递及其研究方法具有强烈的科学兴趣。 体内快速扫描循环伏安法（FSCV）是一种允许以精细的时间和空间分辨率选择性地监测DA浓度变化的方法。这种技术通常用于上升DAergic途径的电刺激以控制多巴胺神经传递的脉冲流动。尽管受刺激的DA神经传递范例可以产生具有清晰形态学的强大的DA反应，使其适合于动力学分析，但仍然存在关于如何根据其DA释放和清除来解释反应的许多争论ce组件。为了解决这个问题，最近开发了一种刺激DA神经传递的定量神经生物学（QN）框架，以在刺激的DA反应过程中实时模拟DA释放和再摄取的动力学。该模型的基础是基于来自刺激的DA神经传递的实验数据和来自各种研究线路的神经传递原理。 QN模型实现了与激发的DA释放和再摄取动力学相关的12个参数以模拟DA响应。这项工作描述了如何使用QNsim1.0模拟DA响应，还详细说明了系统地分辨刺激的多巴胺释放和再摄取动力学变化的原理。

软件程序包括从大鼠背纹纹（研究1）和伏隔核（研究2）获得的样品DA神经传递数据，被编译成“Sample.xlsx”。电子表格包含对DA运输抑制剂哌甲酯（MPH）（10mg / kg）施用35分钟后对60Hz，10s和5s刺激的基线响应的DA浓度数据和对60Hz，5s刺激的响应。 kg，ip）。刺激的DA响应数据被组织成列， 如图3所示 ，其用作用于组织使用软件程序建模的数据的模板。 <p class="jove_content" fo:keep...

Watch this Scientific Journal Video about Modeling Fast-scan Cyclic Voltammetry Data from Electrically Stimulated Dopamine Neurotransmission Data Using QNsim1.0 at JoVE.com

Modeling Fast-scan Cyclic Voltammetry Data from Electrically Stimulated Dopamine Neurotransmission Data Using QNsim1.0

快速扫描循环伏安法可以在药物，疾病和其他实验操作的上下文中监测体内多巴胺神经传递。这项工作描述了QNsim1.0的实现，QNsim1.0是一种根据定量神经生物学模型建模电刺激多巴胺反应的软件，用于量化多巴胺释放和再摄取动力学的估计。

使用QNsim1.0从电刺激多巴胺神经传递数据建模快速扫描循环伏安数据

Central dopaminergic (DAergic) pathways have an important role in a wide range of functions, such as attention, motivation, and movement. Dopamine (DA) is ...

Research

JoVE Journal

Neuroscience

High Density Event-related Potential  Data Acquisition in Cognitive Neuroscience

高密度事件相关电位在认知神经科学的数据采集

Functional magnetic resonance imaging (fMRI) is currently the standard method of evaluating brain function in the field of Cognitive Neuroscience, in part ...

科研

神经科学

Basics of Multivariate Analysis in Neuroimaging Data

多元分析的基础，在影像学资料

Multivariate analysis techniques for neuroimaging data have recently received increasing attention as they have many attractive features that cannot be ...

Presynaptic Dopamine Dynamics in Striatal Brain Slices with Fast-scan Cyclic Voltammetry

突触前多巴胺纹状体脑片的快速扫描循环伏安动态

Extensive research has focused on the neurotransmitter dopamine because of its importance in the mechanism of action of drugs of abuse (e.g. cocaine and ...

Voltage Biasing, Cyclic Voltammetry, &amp; Electrical Impedance Spectroscopy for Neural Interfaces

Voltage Biasing, Cyclic Voltammetry, & Electrical Impedance Spectroscopy for Neural Interfaces

偏置电压，循环伏安，神经接口电阻抗光谱

Electrical impedance spectroscopy (EIS) and cyclic voltammetry (CV) measure properties of the electrode-tissue interface without additional invasive ...

Extracting Visual Evoked Potentials from EEG Data Recorded During fMRI-guided Transcranial Magnetic Stimulation

提取脑电数据视觉诱发电位记录在功能磁共振成像引导下经颅磁刺激

Transcranial Magnetic Stimulation (TMS) is an effective method for establishing a causal link between a cortical area and cognitive/neurophysiological ...

Analyzing Synaptic Modulation of Drosophila melanogaster Photoreceptors after Exposure to Prolonged Light

Analyzing Synaptic Modulation of Drosophila melanogaster Photoreceptors after Exposure to Prolonged Light

分析突触调制<em&gt;果蝇</em&gt;曝光时间延长后，光光感受器

The nervous system has the remarkable ability to adapt and respond to various stimuli. This neural adjustment is largely achieved through plasticity at ...

Analyzing Neural Activity and Connectivity Using Intracranial EEG Data with SPM Software

利用 SPM 软件分析颅内脑电图数据的神经活动和连接性

Measuring neural activity and connectivity associated with cognitive functions at high spatial and temporal resolutions is an important goal in cognitive ...

Data Acquisition and Analysis In Brainstem Evoked Response Audiometry In Mice

脑干中的数据采集与分析 在小鼠中引发响应音频测量

Brainstem evoked response audiometry (BERA) is of central relevance in the clinical neurophysiology. As other evoked potential (EP) techniques, such as ...

Computer-based Multitaper Spectrogram Program for Electroencephalographic Data

基于计算机的多星仪电谱仪程脑电图数据

Current web resources provide limited, user friendly tools to compute spectrograms for visualizing and quantifying electroencephalographic (EEG) data. ...

Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry (CIS-FSCV) to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine

Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry CIS-FSCV to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine

联合输注和刺激与快速扫描循环伏安法（CIS-FSCV）评估腹侧被盖区域受体对相位多巴胺的调节

Phasic dopamine (DA) release from the ventral tegmental area (VTA) to the nucleus accumbens plays a pivotal role in reward processing and reinforcement ...