Cell-specific Synaptic Plasticity in the Auditory Brainstem

听觉脑干中的细胞特异性突触可塑性

• 批准号: 8609018
• 负责人: Thanos Tzounopoulos
• 金额: $ 39.26万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-08 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8609018
• 关键词: Acoustic Nerve; Acoustic Stimulation; Acoustics; Area; Auditory; Auditory system; Biochemical; Brain; Brain Stem; Cells; Endocannabinoids; Environment; Fiber; Genetic; Glutamates; Hippocampus (Brain); Knockout Mice; Link; Mediating; Mus; Neurons; Neurotransmitters; Pattern; Physiological; Probability; Process; Property; Research; Role; Sensory; Signal Pathway; Signal Transduction; Slice; Synapses; Synaptic Vesicles; Synaptic plasticity; System; Techniques; Testing; Time; base; dorsal cochlear nucleus; experience; insight; interest; neurotransmitter release; novel; postsynaptic; presynaptic; receptor; sound

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.

背侧耳蜗核（DCN）是一个听觉的脑干中心，将听觉信号与多模式的感觉信号集成在一起，以帮助方向引起感兴趣的声音。我们以前的研究已经确定了DCN中突触可塑性的许多新型机制，并发现了它们在加工听觉神经输入中的影响。在这里，我们建议研究与谷氨酸固定的“非常规神经递质”的生理作用。 DCN平行纤维末端在其Gluatamataratigic突触囊泡中包含唯一的高水平的Zn [2+]。但是，突触Zn [2+]释放的生理意义在听觉系统中是完全未知的，并且对于其他大脑区域仍然知之甚少。我们假设突触释放的Zn [2+]是听觉系统中的神经递质，可调节DCN神经元的内在和突触性质。为了检验这一假设，我们将采用生理，解剖学和生化技术的组合，这些技术将应用于由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在正常和病理听觉处理过程中涉及的突触和内在机制。