Cell-specific Synaptic Plasticity in the Auditory Brainstem

耳蜗背核（DCN）是一个听觉脑干中心，它将听觉信号与多模态感觉信号相结合，以帮助定位感兴趣的声音。我们之前的研究已经确定了DCN突触可塑性的一些新机制，并揭示了它们在听觉神经输入处理中的影响。在这里，我们建议研究一种与谷氨酸共同释放的“非常规神经递质”的生理作用。DCN平行纤维末端在其谷胱甘肽突触囊泡中含有独特的高水平Zn[2+]。然而，突触Zn[2+]释放对听觉系统的生理意义是完全未知的，对其他脑区也知之甚少。我们假设突触释放的Zn[2+]是听觉系统中的一种神经递质，调节DCN神经元的内在和突触特性。为了验证这一假设，我们将采用生理学、解剖学和生化技术的结合，将其应用于野生型和转基因小鼠制备的脑干切片。阐明这种新型神经递质系统的机制和作用将有助于理解正常和病理听觉加工过程中涉及的突触和内在机制。

The dorsal cochlear nucleus (DCN) is an auditory brainstem center that integrates auditory signals with multimodal sensory signals thought to aid in orientation to sounds of interest. Our previous studies have identified a number of novel mechanisms of synaptic plasticity in the DCN and have uncovered their influence in the processing of auditory nerve inputs. Here, we propose to investigate the physiological role of an "unconventional neurotransmitter" that is coreleased with glutamate. DCN parallel fiber terminals contain uniquely high levels of Zn[2+] in their gluatamatergic synaptic vesicles. However, the physiological significance of synaptic Zn[2+] release is completely unknown for the auditory system and remains poorly understood for other brain areas. We hypothesize that synaptically released Zn[2+] is a neurotransmitter in the auditory system that regulates the intrinsic and synaptic properties of DCN neurons. To test this hypothesis we will employ a combination of physiological, anatomical and biochemical techniques that will be applied to brainstem slices prepared from wild type and genetically modified mice. Elucidating the mechanisms and the roles of this novel neurotransmitter system will contribute significantly towards the understanding of synaptic and intrinsic mechanisms that are involved during normal and pathological auditory processing.