Closed-Loop Characterization of Neuronal Activation Using Electrical Stimulation and Optical Imaging
AbstractWe have developed a closed-loop, high-throughput system that applies electrical stimulation and optical recording to facilitate the rapid characterization of extracellular, stimulus-evoked neuronal activity. In our system, a microelectrode array delivers current pulses to a dissociated neuronal culture treated with a calcium-sensitive fluorescent dye; automated real-time image processing of high-speed digital video identifies the neuronal response; and an optimized search routine alters the applied stimulus to achieve a targeted response. Action potentials are detected by measuring the post-stimulus, calcium-sensitive fluorescence at the neuronal somata. The system controller performs directed searches within the strength–duration (SD) stimulus-parameter space to build probabilistic neuronal activation curves. This closed-loop system reduces the number of stimuli needed to estimate the activation curves when compared to the more commonly used open-loop approach. This reduction allows the closed-loop system to probe the stimulus regions of interest in the multi-parameter waveform space with increased resolution. A sigmoid model was fit to the stimulus-evoked activation data in both current (strength) and pulse width (duration) parameter slices through the waveform space. The two-dimensional analysis results in a set of probability isoclines corresponding to each neuron–electrode pair. An SD threshold model was then fit to the isocline data. We demonstrate that a closed-loop methodology applied to our imaging and micro-stimulation system enables the study of neuronal excitation across a large parameter space. View Full-Text
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Kuykendal, M.L.; Guvanasen, G.S.; Potter, S.M.; Grover, M.A.; DeWeerth, S.P. Closed-Loop Characterization of Neuronal Activation Using Electrical Stimulation and Optical Imaging. Processes 2017, 5, 30.
Kuykendal ML, Guvanasen GS, Potter SM, Grover MA, DeWeerth SP. Closed-Loop Characterization of Neuronal Activation Using Electrical Stimulation and Optical Imaging. Processes. 2017; 5(2):30.Chicago/Turabian Style
Kuykendal, Michelle L.; Guvanasen, Gareth S.; Potter, Steve M.; Grover, Martha A.; DeWeerth, Stephen P. 2017. "Closed-Loop Characterization of Neuronal Activation Using Electrical Stimulation and Optical Imaging." Processes 5, no. 2: 30.