, 2013b). When ChR2 is exposed to blue light, the ion channel opens for exchange of ions,

which creates an action potential across the membrane. As with natural polarization signals, the action potential transfers through the axon to activate the motor plate of the respective muscle that the neuron innervates. For example, some motor neurons in the lumbosacral spinal cord innervate muscles served by the sciatic nerve. To establish the motor function deficit model, a cannula mount is surgically attached to the dorsal aspect of the spinal cord. To test the function of the motor neurons in this area, laser optical fibers are placed into the cannula, and pulses of blue laser light precisely activate motor neurons by opening the light-gated

ChR2. When the lumbosacral-caudal equine of the cord is photoactivated in this way, electromyography (EMG) can be measured on the gastrocnemius or plantar aspect of the hind limbs to monitor Selleckchem CHIR 99021 the photoactivation of the motor neurons. From the data shown in Fig. 2, the blue EMG signal is in exact registration with the optogenetic photoactivation in red (Wang et al., 2013b). The strength or amplitude of the EMG signal can be quantified with the root mean square (RMS) calculation, Selleckchem Z-VAD-FMK and will provide a suitable endpoint to measure therapeutic agents anticipated to treat motor function deficits caused by WNV. When optogenetic photoactivation is performed in transgenic mice infected Fenbendazole intrathecally with WNV, the amplitudes of the EMGs are significantly suppressed compared to transgenic mice receiving sham infection (unpublished data). Although this optogenetics approach requires specialized laser and recording instrumentation committed to the ABSL-3 animal laboratory, the measurements are not subjective evaluations for individual operators as is the MUNE procedure. Moreover, the procedure requires 15 min for each animal as compared to MUNE that requires 1–2 h per animal. As this procedure becomes

refined to obtain longitudinal measurements, investigations on the mechanisms of pathogenesis and treatments for WNV-induced motor function deficits can be investigated. With this model in hand, one could draw on the extensive research and development of candidate drugs used to treat other motor deficit neurological diseases, such as for amyotrophic lateral sclerosis (ALS). For example, Table 2 lists some of the drugs that have been evaluated for ALS treatment (Morrison, 2002), and might in principle be evaluated for treatment of WNV-induced motor function deficits using the described optogenetic photoactivation model. Respiratory distress is a serious outcome of WNND (Sejvar et al., 2005), which can result in respiratory failure with a poor prognosis (Sejvar et al., 2006). Hamster and mouse models have been used to validate that the respiratory distress is caused by neurological deficits (Morrey et al.