A Digital Feedback Clamp Instrument for Neurophysiology

描述（由申请人提供）：电压钳和电流钳技术对理解可兴奋膜中复杂的电流-电压关系做出了重大贡献。最近开发的动态箝位电路在反馈回路中集成了一台计算机，以在电流和电压之间建立数学关系（电导）。我们的目标是开发一种创新的新技术仪器，通用钳，具有增强的神经，肌肉和其他兴奋组织的电生理学研究能力。反馈算法在计算机软件中的实现为电生理学研究提供了一个新的维度，允许创新的实验方案，如复杂的脉冲序列和钳位模式的动态切换。然而，如本提案中的模拟研究所示，计算机引入的处理延迟可能导致显着的性能下降。现有的几种动态钳的实现都是基于现成的设备，没有针对数字反馈进行优化;特别是，它们没有提供足够的频率响应来研究快速动作电位。为了利用数字反馈成功钳位快速动作电位，系统吞吐量需要高达500 KHz至1 MHz。随着更快的数字信号处理（DSP）芯片和适当的控制算法的引入，这种高吞吐量系统最近已经变得可行。因此，本项目旨在开发1）针对可兴奋膜的数字反馈控制进行优化的模拟电子器件; 2）定制的DSP软件，以实现最大化的吞吐量（1 MHz），先进的数字跟踪和易用性;以及3）能够进行电压钳位，电流钳位，电导钳位并形成具有计算机模拟突触的神经元网络的统一多通道系统。在开发过程中，将使用双蔗糖间隙制备物在冲浪蛤的心肌上测试通用钳，并使用两个微电极在池塘蜗牛的脑神经节神经元上测试通用钳。通用钳代表了新一代基于DSP的电生理研究仪器。该仪器将是多功能的，灵活的，具有成本效益的，并将导致神经科学研究的新前沿。拟议的通用夹具中的数字反馈控制也将有助于探索性应用，如脑机接口、假肢设备的神经肌肉控制以及人工感觉替代和植入。

DESCRIPTION (provided by applicant): The techniques of voltage clamp and current clamp have made significant contributions to the understanding of complex current-voltage relations in excitable membranes. The recently developed dynamic clamp incorporates a computer in the feedback loop to impose a mathematical relation (conductance) between current and voltage. Our objective is to develop an innovative new technology instrument, the Universal Clamp, with enhanced capabilities for studying electrophysiology of nerve, muscle, and other excitable tissues. The implementation of feedback algorithms in computer software has provided a new dimension for electrophysiological studies, allowing for innovative experimental protocols such as sophisticated pulse sequencing and dynamic switching of clamp mode. However, as demonstrated by a simulation study in this proposal, processing delay introduced by the computer can result in significant performance degradation. The few existing implementations of dynamic clamps have been based on off-the-shelf devices, not optimized for digital feedback; in particular, they do not provide an adequate frequency response for studying fast action potentials. To successfully clamp a fast action potential with digital feedback, the system throughput needs to be as high as 500 KHz to 1 MHz. Such high-throughput systems have recently become feasible with the introduction of faster digital signal processing (DSP) chips and appropriate control algorithms. Therefore, this project is designed to develop 1) analog electronics optimized for digital feedback control of excitable membranes; 2) customized DSP software for maximized throughput (1 MHz), advanced digital tracking, and ease of use; and 3) a unified multi-channel system capable of voltage clamp, current clamp, conductance clamp, and forming neuronal networks with computer-simulated synapses. During the development, the Universal Clamp will be tested on cardiac muscles of the surf clam with a double-sucrose-gap preparation and cerebral ganglion neurons of the pond snail with two microelectrodes. The Universal Clamp represents a new generation DSP-based instrument for electrophysiological studies. The instrument will be versatile, flexible, and cost-effective; and will lead to new frontiers in neuroscience research. The digital feedback control in the proposed Universal Clamp will also lend itself to exploratory applications such as brain-machine interface, neuromuscular control of prosthetic devices, and artificial sensory replacements and implants.