A Digital Feedback Clamp Instrument for Neurophysiology

描述(申请人提供)：电压钳和电流钳技术对理解可激发膜中复杂的电流-电压关系做出了重大贡献。最近开发的动态钳位在反馈回路中结合了一台计算机，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，通用钳子，具有增强的能力，研究神经、肌肉和其他可兴奋组织的电生理学。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，正如本方案中的模拟研究所表明的那样，计算机引入的处理延迟会导致性能显著下降。现有的几种动态钳位的实现都是基于现成的设备，没有针对数字反馈进行优化；尤其是，它们不能提供足够的频率响应来研究快速动作电位。要使用数字反馈成功钳制快速动作电位，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，这种高通量系统最近变得可行。因此，该项目旨在开发1)针对可兴奋膜的数字反馈控制进行优化的模拟电子产品；2)针对最大吞吐量(1 MHz)、先进的数字跟踪和易用性定制的DSP软件；以及3)能够提供电压钳、电流钳、电导钳并通过计算机模拟突触形成神经网络的统一多通道系统。在研制过程中，将用双蔗糖间隙制剂对万能钳夹进行心肌测试，并用两个微电极对池塘蜗牛的脑神经节神经元进行测试。万能钳是基于数字信号处理器的新一代电生理研究仪器。该仪器将是通用的，灵活的，具有成本效益的；并将引领神经科学研究的新领域。拟议的通用夹具中的数字反馈控制还将用于探索性应用，如脑机接口、假肢设备的神经肌肉控制以及人工感觉替换和植入物。

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.