Imaging Voltage in Genetically Defined Neuronal Subpopulations with a Cre Recombinase-Targeted Hybrid Voltage Sensor

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Genetically encoded voltage indicators (GEVIs) offer a powerful method for observing neuronal electrical activity.
• Targeting GEVIs to specific neuronal populations is crucial for understanding neural circuit function.
• Existing methods require generalized strategies for cell-type-specific probe delivery.

Purpose of the Study:

• To generate a mouse line for efficient, Cre recombinase-dependent expression of an optimized hybrid voltage sensor (hVOS).
• To enable targeted optical monitoring of electrical activity in genetically defined neuronal populations.
• To facilitate the study of neural circuit dynamics and information processing.

Main Methods:

• Generation of a novel mouse line with an optimized hybrid voltage sensor (hVOS) under Cre-dependent control.
• Crossbreeding with Cre driver lines to target hVOS expression in specific interneurons and other neuronal types.
• In vitro imaging experiments in brain slices to record electrically evoked optical signals from multiple neurons.

Main Results:

• Successful expression of hVOS in targeted cell populations, including GABAergic interneurons, mossy cells, and newly born neurons.
• High-fidelity optical recording of action potentials and dendritic integration with submillisecond resolution in single trials.
• Accurate measurement of spike half-widths and identification of trial-to-trial response latency fluctuations.

Conclusions:

• The developed hVOS mouse line provides a versatile tool for cell-type-specific monitoring of neuronal electrical activity.
• Simultaneous, high-temporal-resolution voltage recordings from multiple neurons offer new avenues for studying neural network function.
• This technology enables experimental investigation of how specific neuronal populations contribute to complex circuit computations.