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0 Q&A 572 Views Dec 20, 2025

Optogenetic stimulation of peripheral motor nerves is a promising technique for modulating neural activity via illumination of light-sensitive ion channels known as opsins. Stimulating muscle activity through this method offers many advantages, such as a physiological recruitment order of motor units, reduced fatigue, and target-specific stimulation, which make it a favorable option for use in many neuroscience and motor rehabilitation applications. To enable such optical stimulation, opsin expression in peripheral nerves can be achieved either with transgenic animal models or through injection of viral vectors. In this protocol, we describe a method for driving peripheral nerve opsin expression via intramuscular adeno-associated virus (AAV) injection with the goal of enhancing virus uptake by targeting injections to neuromuscular junctions with electrical stimulation. We also describe procedures for non-invasively assessing functional opsin expression over time with transdermal optical stimulation of opsin-labeled nerves and electromyography (EMG) recordings. The presence of time-locked EMG spikes 4–8 ms after each stimulation pulse demonstrates that functional opsin expression is present at a given assessment time point. Onset of functional optical sensitivity generally occurs 2–4 weeks following virus injection, and sensitivity generally peaks or plateaus between 6–10 weeks. Stimulation sequences such as light intensity, stimulation pulse width, and frequency sweeps provide further information on functional opsin expression at the testing timepoint. The methods presented here can be used for driving functional opsin expression with a standard AAV6 vector commonly used in similar experiments or as a protocol for assessing peripheral nerve opsin expression with novel viral vectors.

0 Q&A 2092 Views Aug 5, 2023

Sleep is not homogenous but contains a highly diverse microstructural composition influenced by neuromodulators. Prior methods used to measure neuromodulator levels in vivo have been limited by low time resolution or technical difficulties in achieving recordings in a freely moving setting, which is essential for natural sleep. In this protocol, we demonstrate the combination of electroencephalographic (EEG)/electromyographic (EMG) recordings with fiber photometric measurements of fluorescent biosensors for neuromodulators in freely moving mice. This allows for real-time assessment of extracellular neuromodulator levels during distinct phases of sleep with a high temporal resolution.




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