Optogenetic control of contractile function in skeletal muscle

Abstract

Optogenetic stimulation allows activation of cells with high spatial and temporal precision. Here we show direct optogenetic stimulation of skeletal muscle from transgenic mice expressing the light-sensitive channel Channelrhodopsin-2 (ChR2). Largest tetanic contractions are observed with 5-ms light pulses at 30 Hz, resulting in 84% of the maximal force induced by electrical stimulation. We demonstrate the utility of this approach by selectively stimulating with a light guide individual intralaryngeal muscles in explanted larynges from ChR2-transgenic mice, which enables selective opening and closing of the vocal cords. Furthermore, systemic injection of adeno-associated virus into wild-type mice provides sufficient ChR2 expression for optogenetic opening of the vocal cords. Thus, direct optogenetic stimulation of skeletal muscle generates large force and provides the distinct advantage of localized and cell-type-specific activation. This technology could be useful for therapeutic purposes, such as restoring the mobility of the vocal cords in patients suffering from laryngeal paralysis.

Stretchable and Transparent Biointerface Using Cell‐Sheet–Graphene Hybrid for Electrophysiology and Therapy of Skeletal Muscle

“…The light intensity before and after passing through the device is shown in Figure S16 in the Supporting Information, which is high enough to stimulate deep muscles. [ 60 ] Optical stimulationinduced muscle activation and EMG signals are recorded simultaneously (40 Hz, 464 mW m −2 fi xed; Figure 6 …”

“…Optimized conditions of the light impulses for maximum excitation of peripheral motor neurons are experimentally determined through recording EMG signals under different light frequencies and intensities. [ 21,60 ] Figure 6 e shows the processed EMG signals to present their amplitudes [ 61 ] under different frequencies (464 mW m −2 is fi xed) of light impulses applied to hind limb muscles (fi ltered EMG shown in Figure S17 in the Supporting Information). We found that 40 Hz optical stimulation shows the highest amplitude of EMG.…”

“…The plateau potential increases as the frequency of optical stimulation increases ( Figure S17, Supporting Information). [ 60 ] The amplitude of EMG signal at the frequency of 80 Hz, however, is decreased because the depolarization continues from the delay of repolarization. [ 60 ] Figure 6 f shows the processed EMG signals of different light intensities (40 Hz is fi xed) ranging from 8 to 464 mW m −2 (fi ltered EMG shown in Figure S18 in the Supporting Information).…”

Restoring motor function using optogenetics and neural engraftment

“…Finally, a recent development in terms of using optogenetics to control muscle function is the use of direct optogenetic control of muscle contraction, using both transgenic ChR2 expressing mice and viral transduction of muscle in vivo, to optically control the muscles of the larynx [46]. This approach may provide a complementary therapy to prevent muscle wasting in the intervening period between muscle denervation and reinnervation by regenerating axons [47].…”

Viral-mediated optogenetic stimulation of peripheral motor nerves in non-human primates

“…A more commonly used approach in line with gene therapy approaches used in other systems and disease models [24] is the utilization of adeno-associated virus (AAV) vectors to enable optical modulation of muscle activity. These include expression of ChR2 in rat peripheral motor nerves following muscle injection of an AAV vector [18,25] or expression directly in mouse skeletal muscle tissue following systemic injection [26]. While direct optical modulation of muscle tissue is feasible, it would require individual light sources for each targeted muscle, and implanting optical stimulation hardware could be difficult in smaller or deep muscles such as intrinsic hand muscles.…”