■主观性耳鸣,没有外部声源的声音感知,通常是在噪声引起的听力损失或耳毒性药物之后。这种情况被认为是由听觉中枢的神经可塑性改变引起的,由于兴奋和抑制之间的不平衡,其特征是自发神经活动增强和同步性增强。然而,丘脑网状核(TRN)的作用,由参与丘脑皮质振荡的GABA能神经元组成的结构,在耳鸣的发病机理上仍未被探讨。
■我们使用水杨酸钠在小鼠中诱导耳鸣,并使用声惊厥的间隙前脉冲抑制(GPIAS)范例评估耳鸣样行为。我们利用组合的病毒追踪技术来识别所涉及的神经回路,并采用免疫荧光和共聚焦成像来确定细胞类型和激活的神经元。
■水杨酸处理的小鼠表现出耳鸣样行为。我们的追踪清楚地描绘了听觉特定TRN的输入和输出。我们发现听觉TRN的化学遗传激活显着降低了水杨酸引起的听觉皮层c-Fos表达的升高。
■这一发现认为TRN是耳鸣治疗的潜在调节靶标。此外,映射到听觉TRN的感觉输入提示了使用光遗传学或感觉刺激来操纵丘脑皮质活动的可能性。听觉TRN介导的神经通路的精确映射为设计有针对性的干预措施以减轻耳鸣症状提供了有希望的途径。
UNASSIGNED: Subjective tinnitus, the perception of sound without an external acoustic source, is often subsequent to noise-induced hearing loss or ototoxic medications. The condition is believed to result from neuroplastic alterations in the auditory centers, characterized by heightened spontaneous neural activities and increased synchrony due to an imbalance between excitation and inhibition. However, the role of the thalamic reticular nucleus (TRN), a structure composed exclusively of GABAergic neurons involved in thalamocortical oscillations, in the pathogenesis of tinnitus remains largely unexplored.
UNASSIGNED: We induced tinnitus in mice using sodium salicylate and assessed tinnitus-like behaviors using the Gap Pre-Pulse Inhibition of the Acoustic Startle (GPIAS) paradigm. We utilized combined viral tracing techniques to identify the neural circuitry involved and employed immunofluorescence and confocal imaging to determine cell types and activated neurons.
UNASSIGNED: Salicylate-treated mice exhibited tinnitus-like behaviors. Our tracing clearly delineated the inputs and outputs of the auditory-specific TRN. We discovered that chemogenetic activation of the auditory TRN significantly reduced the salicylate-evoked rise in c-Fos expression in the auditory cortex.
UNASSIGNED: This finding posits the TRN as a potential modulatory target for tinnitus treatment. Furthermore, the mapped sensory inputs to the auditory TRN suggest possibilities for employing optogenetic or sensory stimulations to manipulate thalamocortical activities. The precise mapping of the auditory TRN-mediated neural pathways offers a promising avenue for designing targeted interventions to alleviate tinnitus symptoms.