Low-intensity focused ultrasound stimulation (LIFUS) has the potential to noninvasively penetrate the intact skull and to modulate neural activity in the cortex and deep brain nuclei. The midbrain periaqueductal gray (PAG) is associated with the generation of defensive behaviors. The aim of this study was to examine whether LIFUS of the PAG induced defensive behaviors in mice. A 3.8-MHz head-mounted ultrasound transducer with a small focus size (0.5 mm $\,\,\times $ 0.5 mm) was fabricated in house to precisely stimulate the free-moving mice. The corresponding behaviors were recorded in real time. Avoidance, flight, and freezing were used to assess ultrasound-induced defensive responses. The safety of LIFUS was examined via hematoxylin and eosin (H&E) staining and Nissl staining. Ultrasound stimulation of the PAG induced multiple defensive behaviors, including location-specific passive avoidance behavior, flight, and freezing. In addition, H&E and Nissl staining verified that LIFUS did not cause any injury to the brain tissue. These findings demonstrate that LIFUS may have neuromodulatory effects on the innate defensive behaviors in mice. LIFUS may be used as a novel neuromodulatory tool for the treatment of psychological diseases associated with defensive behaviors.

中文翻译：

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超声刺激导水管周围灰质诱导防御行为。

低强度聚焦超声刺激 (LIFUS) 具有无创穿透完整颅骨并调节皮质和深部脑核中的神经活动的潜力。中脑导水管周围灰质 (PAG) 与防御行为的产生有关。本研究的目的是检查 PAG 的 LIFUS 是否会诱导小鼠的防御行为。一个 3.8-MHz 头戴式超声换能器，具有小焦点尺寸（0.5 毫米 $\,\,\times $ 0.5 毫米）是在内部制造的，以精确刺激自由移动的小鼠。相应的行为被实时记录。回避、逃跑和冻结被用来评估超声引起的防御反应。通过苏木精和伊红 (H&E) 染色和 Nissl 染色检查 LIFUS 的安全性。PAG 的超声刺激诱导多种防御行为，包括特定位置的被动回避行为、飞行和冻结。此外，H&E 和 Nissl 染色证实 LIFUS 不会对脑组织造成任何伤害。这些发现表明 LIFUS 可能对小鼠的先天防御行为具有神经调节作用。LIFUS 可用作治疗与防御行为相关的心理疾病的新型神经调节工具。