Munoz Felipe, Vicencio-Jimenez Sergio, Jorratt Pascal, Delano Paul H, Terreros Gonzalo
Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile.
Universidad de Valparaíso, Valparaíso, Chile.
Front Neurosci. 2022 Apr 27;16:866161. doi: 10.3389/fnins.2022.866161. eCollection 2022.
Cholinergic transmission is essential for survival and reproduction, as it is involved in several physiological responses. In the auditory system, both ascending and descending auditory pathways are modulated by cholinergic transmission, affecting the perception of sounds. The auditory efferent system is a neuronal network comprised of several feedback loops, including corticofugal and brainstem pathways to the cochlear receptor. The auditory efferent system's -final and mandatory synapses that connect the brain with the cochlear receptor- involve medial olivocochlear neurons and outer hair cells. A unique cholinergic transmission mediates these synapses through α9/α10 nicotinic receptors. To study this receptor, it was generated a strain of mice carrying a null mutation of the Chrna9 gene (α9-KO mice), lacking cholinergic transmission between medial olivocochlear neurons and outer hair cells, providing a unique opportunity to study the role of medial olivocochlear cholinergic transmission in auditory and cognitive functions. In this article, we review behavioral and physiological studies carried out to research auditory efferent function in the context of audition, cognition, and hearing impairments. Auditory studies have shown that hearing thresholds in the α9-KO mice are normal, while more complex auditory functions, such as frequency selectivity and sound localization, are altered. The corticofugal pathways have been studied in α9-KO mice using behavioral tasks, evidencing a reduced capacity to suppress auditory distractors during visual selective attention. Finally, we discuss the evolutionary role of the auditory efferent system detecting vocalizations in noise and its role in auditory disorders, such as the prevention of age-related hearing loss.
胆碱能传递对于生存和繁殖至关重要，因为它参与多种生理反应。在听觉系统中，胆碱能传递对听觉的上行和下行通路均有调节作用，从而影响声音的感知。听觉传出系统是一个由多个反馈回路组成的神经网络，包括通向耳蜗感受器的皮质离心和脑干通路。听觉传出系统与耳蜗感受器相连的最终且必经的突触涉及内侧橄榄耳蜗神经元和外毛细胞。一种独特的胆碱能传递通过α9/α10烟碱样受体介导这些突触。为了研究这种受体，构建了一种携带Chrna9基因无效突变的小鼠品系（α9基因敲除小鼠），该品系在内侧橄榄耳蜗神经元和外毛细胞之间缺乏胆碱能传递，为研究内侧橄榄耳蜗胆碱能传递在听觉和认知功能中的作用提供了独特的机会。在本文中，我们综述了为研究听觉传出功能在听觉、认知和听力障碍背景下所开展的行为学和生理学研究。听觉研究表明，α9基因敲除小鼠的听力阈值正常，而频率选择性和声音定位等更复杂的听觉功能则发生了改变。利用行为任务对α9基因敲除小鼠的皮质离心通路进行了研究，结果表明在视觉选择性注意过程中抑制听觉干扰物的能力下降。最后，我们讨论了听觉传出系统在噪声中检测发声的进化作用及其在听觉障碍（如预防年龄相关性听力损失）中的作用。
