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.

I. Introduction

Neurological and psychiatric disorders such as Parkinson's disease, epilepsy, and depression affect many people [1]. Neuromodulation is a well-known method that involves the use of chemical, electrical, magnetic, thermal, and optical stimulation [2]. However, these therapeutic methods have various disadvantages [3] such as drug reactions to pharmacotherapy [4], limited penetration depth and spatial resolution of transcranial current and magnetic stimulation, and the invasiveness of deep brain stimulation, which have motivated explorations of other neuromodulation methods [5]–[7].