Real Time NEURON Simulation for Experimental Applications

该提案的目标是联合收割机NEURON数学建模软件的功能与 Cybercyte“即插即用”动态夹紧系统。我们的产品将使所有神经元电生理学家， 能够执行基于复杂NEURON模型的动态箝位实验，而无需 编程、工程或数学建模技能。我们的产品是一个集成的硬件包 和专门用于神经科学应用的软件，专注于所需的特定稳定性和可靠性 用于常规神经元电生理学和神经系统中发现的大量离子通道。四 该项目的目标是： 目标1.实施和测试电子表达模式。在这个目标中，膜片钳放大器被用于 电流钳模式运行活细胞的细胞为基础的动作电位，与计算机模型增强， 具体渠道。由计算机模型产生的人工离子通道用于注入等效电流 为了模拟通道突变、功能获得、状态依赖性药物结合等的作用，透露他们的 对真实的神经元兴奋性的作用机制。这可以被认为是一种廉价的“捷径”， 创建离子通道遗传模型和其他电生理模型的艰苦过程。 目标2.实施和测试合成细胞模式。在合成细胞模式下，所有的分量电流，除了 对于感兴趣的一个，沿着与膜动作电位一起建模。那么，利息流是 在例如表达感兴趣通道的HEK细胞中产生，并由电压钳控制 增幅器电压钳的指令输入是来自动态钳的模拟动作电位 合成细胞系统。例如，可以将真实的药物添加到感兴趣的克隆通道或克隆通道中。 可以分析真实的动力学突变的结果。 目标3.实现并演示电池耦合模式。细胞耦合模式可以说是第一种形式的 发明了动态钳。最初，它使用模拟电路来模拟细胞之间的间隙连接电阻。 有了NEURON，我们可以实现复杂形式的细胞与细胞耦合，包括突触传递， 中间神经元。 目标4。实施和测试诊断和实验保障措施。动态箝位的一个主要局限性 在研究和开发中的应用，特别是在商业应用中， 质量控制这一目标有助于自动化的质量控制过程，使系统访问非- 专业用户。 这些目标的完成将导致一个商业先进的动态夹持系统的接口， NEURON，功能强大，可靠，但即插即用安装，使用简单。

The goal of this proposal is to combine the power of the NEURON mathematical modeling software with the Cybercyte “plug and play” dynamic clamp system. Our product will enable all neuronal electrophysiologists to be able to perform sophisticated NEURON model based dynamic clamp experiments, without any requirement for programming, engineering, or mathematical modeling skills. Our product is an integrated package of hardware and software specifically for neuroscience applications, focusing on the specific stability and reliability needed for routine neuronal electrophysiology and the large array of ion channels found in the nervous system. The four aims of this project are: Aim 1. Implement and Test Electronic Expression Mode. In this aim, the patch clamp amplifier is used in current clamp mode to run cell-based action potentials from live cells, augmented with computer models of specific channels. Artificial ion channels generated by computer models are used to inject an equivalent current to mimic the effects of channel mutations, gain of function, state dependent drug binding etc., to reveal their mechanisms of action on the excitability of real neurons. This can be thought of as an inexpensive “short cut” to the painstaking process of generating genetic models of ion channels and other electrophysiological models. Aim 2. Implement and Test Synthetic Cell Mode. In synthetic cell mode, all of the component currents, except for the one of interest, are modelled, along with membrane action potentials. The current of interest is then generated in, for example, an HEK cell expressing the channel of interest and controlled by a voltage-clamp amplifier. The command input to the voltage clamp is the simulated action potential from the dynamic clamp system with the synthetic cell. For example, real drugs can be added to the cloned channel of interest or the consequences of a real kinetic mutation can be analyzed. Aim 3. Implement and Demonstrate Cell Coupling Mode. Cell coupling mode was arguably the first form of dynamic clamp invented. Originally it used analog circuitry to mimic gap junctional resistance between cells. With NEURON, we can implement complex forms of cell to cell coupling, including synaptic transmission and interneurons. Aim 4. Implement and Test Diagnostics and Experimental Safeguards. A major limitation of dynamic clamp applications in research & development, particularly in commercial applications, is the difficulty in maintaining quality control. This aim helps automate the process of quality control to make the system accessible to non- specialist users. Completion of these aims will result in a commercial advanced dynamic clamp system with an interface to NEURON, which is powerful, reliable, but plug and play to install, and simple to use.