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

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.