Frequency Dependence of Ultrasound Neurostimulation in the Mouse Brain.

Ultrasound neuromodulation holds promise as a non-invasive technique for neuromodulation of the central nervous system. However, much remains to be determined about how the technique can be transformed into a useful technology, including the effect of ultrasound frequency. Previous studies have demonstrated neuromodulation in vivo using frequencies <1 MHz, with a trend toward improved efficacy with lower frequency. However, using higher frequencies could offer improved ultrasound spatial resolution. We investigate the ultrasound neuromodulation effects in mice at various frequencies both below and above 1 MHz. We find that frequencies up to 2.9 MHz can still be effective for generating motor responses, but we also confirm that as frequency increases, sonications require significantly more intensity to achieve equivalent efficacy. We argue that our results provide evidence that favors either a particle displacement or a cavitation-based mechanism for the phenomenon of ultrasound neuromodulation.

Localization of ultrasound-induced in vivo neurostimulation in the mouse model.

Developments in the use of ultrasound to stimulate and modulate neural activity have raised the possibility of using ultrasound as a new investigative and therapeutic tool in brain research. Although the phenomenon of ultrasound-induced neurostimulation has a long history dating back many decades, until now there has been little evidence of a clearly localized effect in the brain, a necessary requirement for the technique to become genuinely useful. Here we report clearly distinguishable effects in sonicating rostral and caudal regions of the mouse motor cortex. Motor responses measured by normalized electromyography in the neck and tail regions changed significantly when sonicating the two different areas of motor cortex. Response latencies varied significantly according to sonication location, suggesting that different neural circuits are activated depending on the precise focus of the ultrasound beam. Taken together, our findings present good evidence of the ability to target selective parts of the motor cortex with ultrasound neurostimulation in the mouse, an advance that should help to set the stage for developing new applications in larger animal models, including humans.

Effective parameters for ultrasound-induced in vivo neurostimulation.

Ultrasound-induced neurostimulation has recently gained increasing attention, but little is known about the mechanisms by which it affects neural activity or about the range of acoustic parameters and stimulation protocols that elicit responses. We have established conditions for transcranial stimulation of the nervous system in vivo, using the mouse somatomotor response. We report that (1) continuous-wave stimuli are as effective as or more effective than pulsed stimuli in eliciting responses, and responses are elicited with stimulus onset rather than stimulus offset; (2) stimulation success increases as a function of both acoustic intensity and acoustic duration; (3) interactions of intensity and duration suggest that successful stimulation results from the integration of stimulus amplitude over a time interval of 50 to 150 ms; and (4) the motor response elicited appears to be an all-or-nothing phenomenon, meaning stronger stimulus intensities and durations increase the probability of a motor response without affecting the duration or strength of the response.

Genetic dissection reveals two separate retinal substrates for polarization vision in Drosophila.

BACKGROUND: Linearly polarized light originates from atmospheric scattering or surface reflections and is perceived by insects, spiders, cephalopods, crustaceans, and some vertebrates. Thus, the neural basis underlying how this fundamental quality of light is detected is of broad interest. Morphologically unique, polarization-sensitive ommatidia exist in the dorsal periphery of many insect retinas, forming the dorsal rim area (DRA). However, much less is known about the retinal substrates of behavioral responses to polarized reflections. SUMMARY: Drosophila exhibits polarotactic behavior, spontaneously aligning with the e-vector of linearly polarized light, when stimuli are presented either dorsally or ventrally. By combining behavioral experiments with genetic dissection and ultrastructural analyses, we show that distinct photoreceptors mediate the two behaviors: inner photoreceptors R7+R8 of DRA ommatidia are necessary and sufficient for dorsal polarotaxis, whereas ventral responses are mediated by combinations of outer and inner photoreceptors, both of which manifest previously unknown features that render them polarization sensitive. CONCLUSIONS: Drosophila uses separate retinal pathways for the detection of linearly polarized light emanating from the sky or from shiny surfaces. This work establishes a behavioral paradigm that will enable genetic dissection of the circuits underlying polarization vision.