Noninvasive Ultrasonic Neuromodulation in Freely Moving Mice.

Neuromodulation is a fundamental method for obtaining basic information about neuronal circuits for use in treatments for neurological and psychiatric disorders. Ultrasound stimulation has become a promising approach for noninvasively inducing neuromodulation in animals and humans. However, the previous investigations were subject to substantial limitations, due to most of them involving anesthetized and fixed small-animal models. Studies of awake and freely moving animals are needed, but the currently used ultrasound devices are too bulky to be applied to a freely moving animal. This study is the first time to design and fabricate a miniature and lightweight head-mounted ultrasound stimulator for inducing neuromodulation in freely moving mice. The main components of the stimulator include a miniature piezoelectric ceramic, a concave epoxy acoustic lens, and housing and connection components. The device was able to induce action potentials recorded in situ and evoke head-turning behaviors by stimulating the primary somatosensory cortex barrel field of the mouse. These findings indicate that the proposed method can be used to induce noninvasive neuromodulation in freely moving mice. This novel method could potentially lead to the application of ultrasonic neuromodulation in more-extensive neuroscience investigations.

Imaging-Guided Dual-Target Neuromodulation of the Mouse Brain Using Array Ultrasound.

Neuromodulation is an important method for investigating neural circuits and treating neurological and psychiatric disorders. Multiple-target neuromodulation is considered an advanced technology for the flexible optimization of modulation effects. However, traditional methods such as electrical and magnetic stimulations are not convenient for multiple-target applications due to their disadvantages of invasiveness or poor spatial resolution. Ultrasonic neuromodulation is a new noninvasive method that has gained wide attention in the field of neuroscience, and it is potentially able to support multiple-target stimulation by allocating multiple focal points in the brain using an array transducer. However, there are no reports in the literature of the efficacy of this technical concept, and an imaging tool for localizing the stimulation area for evaluating the neural effects in vivo has been lacking. In this study, we designed and fabricated a new system specifically for imaging-guided dual-target neuromodulation. The design of the array transducer and overall system is described in detail. The stimulation points were selectable on a B-mode image. In vivo experiments were carried out in mice, in which forelimbs shaking responses and electromyography outcomes were induced by changing the stimulation targets. The system could be a valuable tool for imaging-guided multiple-target stimulation in various neuroscience applications.

Cortex phellodendri Extract Relaxes Airway Smooth Muscle.

Cortex phellodendri is used to reduce fever and remove dampness and toxin. Berberine is an active ingredient of C. phellodendri. Berberine from Argemone ochroleuca can relax airway smooth muscle (ASM); however, whether the nonberberine component of C. phellodendri has similar relaxant action was unclear. An n-butyl alcohol extract of C. phellodendri (NBAECP, nonberberine component) was prepared, which completely inhibits high K(+)- and acetylcholine- (ACH-) induced precontraction of airway smooth muscle in tracheal rings and lung slices from control and asthmatic mice, respectively. The contraction induced by high K(+) was also blocked by nifedipine, a selective blocker of L-type Ca(2+) channels. The ACH-induced contraction was partially inhibited by nifedipine and pyrazole 3, an inhibitor of TRPC3 and STIM/Orai channels. Taken together, our data demonstrate that NBAECP can relax ASM by inhibiting L-type Ca(2+) channels and TRPC3 and/or STIM/Orai channels, suggesting that NBAECP could be developed to a new drug for relieving bronchospasm.