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: 8429374
• 负责人: Thanos Tzounopoulos
• 金额: $ 37.29万
• 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/8429374
• 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.

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整合在一起，被认为有助于对感兴趣的声音进行定向。我们以前的研究已经确定了一些新的机制，突触可塑性的DCN，并揭示了他们的影响，在处理听觉神经输入。在这里，我们建议调查的生理作用的“非传统的神经递质”，是coreleased与谷氨酸。DCN平行纤维末端在其谷氨酸能突触小泡中含有独特的高水平Zn[2+]。然而，突触Zn[2+]释放的生理意义对于听觉系统是完全未知的，对于其他脑区仍然知之甚少。我们假设突触释放的Zn[2+]是听觉系统中调节DCN神经元内在和突触特性的神经递质。为了验证这一假设，我们将采用生理学，解剖学和生物化学技术的组合，将适用于从野生型和转基因小鼠制备的脑干切片。阐明这种新的神经递质系统的机制和作用将有助于对正常和病理听觉过程中所涉及的突触和内在机制的理解显着。