Improved Monitoring of Single Unit Activity in Neuronal Circuits by Localization of a Hybrid Optical Voltage Sensor to the Soma



Bolton, Allison N

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Electrical activity of neurons traditionally has been measured using electrophysiological methods. In this manner, numerous important concepts regarding relationships between activity dynamics in neuronal circuits and cognitive abilities have been resolved. However, a technological ceiling has been reached in trying to apply electrophysiological recordings to monitor large numbers of neurons simultaneously as an animal performs a behavioral task, limiting further discoveries. Voltage- and calcium-sensitive dyes (VSDs) proved successful in increasing the recording throughput, providing the impetus to develop genetically encoded probes. Genetically encoded voltage and calcium sensors allow for cellular specificity with a few constructs displaying the temporal resolution required to track action potentials (APs) in neural circuits, including the hybrid optical voltage sensor (hVoS) system. The poor signal-to-noise ratio, due to cell-wide expression, limits the specificity of neuronal recordings, leading us to develop a novel hVoS sensor (termed Firefluo) where the membrane-anchored fluorescent protein is fused to the carboxy terminus of the SK1 potassium channel, directing surface expression to the neuronal soma only. It is believed that Firefluo will greatly increase the signal-to-noise ratio for AP dynamics in large neuronal populations by removing background noise from neuronal processes and more tightly coupling the fluorophore to APs due to it’s soma localization.



Hybrid optical voltage sensors, Optical imaging, Soma localization, FireFlou, Voltage imaging