Meng Degong, Zhang Cong, Pei Jiamin, Zhang Xiao, Lu Hanna, Ji Hui, Zhang Xiangjian, Yuan Yi
School of Electrical Engineering, Yanshan University, Qinhuangdao 066004, China; Key Laboratory of Intelligent Rehabilitation and Neuromodulation of Hebei Province, Yanshan University, Qinhuangdao 066004, China.
Department of Neurology, the Second Hospital of Hebei Medical University, Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, China.
Neuroimage. 2025 Oct 1;319:121441. doi: 10.1016/j.neuroimage.2025.121441. Epub 2025 Sep 1.
Synaptic plasticity plays a crucial role in the extinction of fearful memories. Low-intensity transcranial ultrasound stimulation (TUS) can modulate synaptic plasticity and promote the extinction of fear memories. However, the mechanism by which TUS promotes the extinction of fear memory remains unclear. This study aimed to explore whether and how synaptic plasticity under TUS is involved in modulating fear memory and the role of the brain-derived neurotrophic factor (BDNF)-the tropomyosin-related kinase B (TrkB) signaling pathway in this process. We used behavioral tests and two-photon fluorescence imaging to investigate the modulatory effects of TUS on fear memory and examined the formation/elimination of dendritic spines and the calcium activity of pyramidal neurons in the prefrontal cortex in mice in vivo. We found that TUS of the prefrontal cortex can promote fear memory extinction in mice while promoting dendritic spine formation, reducing dendritic spine elimination, increasing pyramidal neuron activity, and enhancing the expression of BDNF and its receptor TrkB. Conversely, inhibiting the BDNF-TrkB signaling pathway weakened these effects of ultrasound stimulation. Our study demonstrated that TUS could promote the extinction of fear memories, indicating that TUS has the potential to be used in the clinical treatment of patients with fear memory.
突触可塑性在恐惧记忆的消退中起着至关重要的作用。低强度经颅超声刺激（TUS）可以调节突触可塑性并促进恐惧记忆的消退。然而，TUS促进恐惧记忆消退的机制仍不清楚。本研究旨在探讨TUS作用下的突触可塑性是否以及如何参与调节恐惧记忆，以及脑源性神经营养因子（BDNF）-原肌球蛋白相关激酶B（TrkB）信号通路在此过程中的作用。我们使用行为测试和双光子荧光成像来研究TUS对恐惧记忆的调节作用，并在体内检测小鼠前额叶皮质中树突棘的形成/消除以及锥体神经元的钙活性。我们发现，前额叶皮质的TUS可以促进小鼠恐惧记忆的消退，同时促进树突棘的形成，减少树突棘的消除，增加锥体神经元的活性，并增强BDNF及其受体TrkB的表达。相反，抑制BDNF-TrkB信号通路会削弱超声刺激的这些作用。我们的研究表明，TUS可以促进恐惧记忆的消退，这表明TUS有潜力用于恐惧记忆患者的临床治疗。
