Simultaneous high-density mapping of synaptic neurochemical transmissions and action potential in a large neural network

神经元的兴奋产生动作电位，动作电位通过神经元体和轴突向突触传播。利用神经元培养物的大型微电极阵列进行电位记录已被广泛用于监测神经尖峰活动和细胞活动。然而，这种方法不监测神经化学物质的释放，因此只包含关于突触神经传递的间接信息。神经尖峰活动与神经递质分泌相关；然而，由于复杂的囊泡运输和胞吐过程，一个不能用来预测另一个。由于许多神经退行性疾病，包括阿尔茨海默病和帕金森病，在神经元丧失之前干扰和调节突触功能，理想情况下，这项新技术应该能够监测神经脉冲活动和突触释放神经化学物质的动态。该项目的中心目标是满足这一未满足的需求。该项目的教育目标是通过多维方法在缩小科学和工程领域的知识和兴趣差距方面发挥令人兴奋的作用。该教育计划预计将(i)提高公众的科学素养，（ii）吸引STEM中代表性不足的学生群体，以及（iii）提供高要求的课程，为学生在新兴的神经工程领域做好准备。该项目的目标是开发一种新的神经化学-电生理传感器技术，可以同时监测神经化学和神经尖峰活动。神经化学-电生理传感器将能够全面研究突触功能，从通过轴突传播的动作电位（AP）到在突触上快速唤起神经化学事件，这些事件导致神经递质在细胞外释放。新的神经化学-电生理学技术将提供无标记、多位点和长期的神经突触传递活动监测，因此，能够表征生理条件和神经退行性疾病中的突触功能。该项目的研究计划有三个目标：(1)开发具有快速扫描循环伏安图（FSCV）能力的高密度神经化学-电生理放大器；(2)开发片上16384微电极阵列，研究开关矩阵连通性；(3)应用神经化学-电生理学技术监测来自大型神经网络的突触传递。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The excitation of neurons results in action potentials, which propagates through the neuronal body and axons toward synapses. The electrical potential recordings using a large microelectrode array from neuronal cultures has been widely used to monitor neural spike activities and cellular activities. However, this approach does not monitor neurochemical release, and therefore only contains indirect information regarding synaptic neurotransmission. The neural spike activities and the neurotransmitter secretions are related; however, one cannot be used to predict the other because of the complex vesicle trafficking and exocytosis processes. Because many neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease, interfere and modulate synaptic functions prior to neuronal loss, ideally, the new technology should be able to monitor the dynamics of both neural spike activities and neurochemical release from synapses. The central objective of this project is to serve this unmet need. The educational objective of this project is to lead an exciting role in closing the knowledge and interest gaps in science and engineering via a multidimensional approach. The education program is expected to (i) increase public scientific literacy, (ii) engage underrepresented student groups in STEM, and (iii) provide a highly demanded curriculum to prepare students in the emerging field of neural engineering. The goal of this project is to develop a novel neurochemical-electrophysiology sensor technology that can simultaneously monitor neurochemical and neural spike activities. The neurochemical-electrophysiology sensor will enable the comprehensive investigation of synaptic function from action potential (AP) propagating through the axon to rapidly evoking neurochemical events at the synapses which cause the extracellular release of neurotransmitters. The new neurochemical-electrophysiology technology will provide label-free, multisite, and long-term monitoring of neuronal synaptic transmission activities, hence, enabling the characterization of synaptic function in physiological conditions and neurodegenerative disorders. The project's Research Plan is organized under three aims: (1) Develop high-density neurochemical-electrophysiology amplifiers with fast-scan cyclic voltammogram (FSCV) capability; (2) Develop on-chip 16,384 microelectrode array and investigate switch-matrix connectivity; and (3) Apply the neurochemical-electrophysiology technology to monitor synaptic transmission from a large neural network.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.