Neuronal ensembles during development of tonotopic maps in the auditory system

 描述（由申请人提供）：音调是听觉系统中声音频率的地图式表示。先前的电生理学研究从这项研究和其他人的工作确定了一个精确的模式，自发动作电位爆发听觉神经元的内侧核的斜方体（MNTB），起源于未成熟的耳蜗。自发性动作电位爆发对于听力开始前的短时突触可塑性和听觉突触连接的精细化是重要的。然而，整体自发活动的tonotopic地图的细胞机制仍然不清楚。为了解决这一科学问题，将用钙指示剂来测量细胞活性，钙指示剂是一种响应细胞内钙离子浓度变化而发出荧光的分子。使用最先进的荧光双光子显微镜，将有可能在不同发育阶段以细胞分辨率测量麻醉啮齿动物幼仔活脑中的钙信号。总体假设是，活动依赖性机制，局部细胞相互作用和经验相互作用，以确定在听觉系统发育的合奏地图活动的模式。其目标是：1）确定MNTB中神经元整体活动的发育模式; 2）确定MNTB中星形胶质细胞分化和活动的发育模式;以及3）确定母亲护理、听觉发育和MNTB听觉地图活动之间的关系。总之，这些研究将确定神经胶质细胞在哺乳动物中枢听觉回路成熟中的作用，并增加神经胶质细胞在哺乳动物中枢听觉回路成熟中的作用。 我们对经验和内在程序如何相互作用以产生听觉系统的发育可塑性的理解。听觉障碍如耳聋是由耳朵的不同细胞和分子成分的缺陷引起的。然而，最近的证据表明，听觉系统中的中枢神经系统功能障碍有助于神经精神疾病和其他形式的神经系统疾病的发育发作。这项提案中的工作将定义大脑听觉地图的活动模式在发育过程中如何变化，为理解这些模式如何在自闭症和精神分裂症等疾病中受到影响提供线索。

 DESCRIPTION (provided by applicant): Tonotopy is the map-like representation of sound frequency in the auditory system. Previous electrophysiology studies from this research and the work of others identified a precise pattern of spontaneous action potential bursts in auditory neurons of the medial nucleus of the trapezoid body (MNTB) that originates in the immature cochlea. Spontaneous action potential bursts are important for short-term synaptic plasticity and refinement of auditory synaptic connections before the onset of hearing. However, the cellular mechanisms of ensemble spontaneous activity in tonotopic maps remain unclear. To address this scientific issue, cellular activity will be measured with calcium indicators, molecules that emit fluorescence in response to changes in intracellular calcium ion concentration. Using state-of-the-art fluorescence two-photon microscopy it will be possible to measure calcium signals in the living brain of anesthetized rodent pups with cellular resolution at different stages of development. The overall hypothesis is that activity-dependent mechanisms, local cellular interactions and experience interact to determine the patterns of ensemble map activity during auditory system development. The aims are: 1) To define developmental patterns of neuronal ensemble activity in the MNTB; 2) To define developmental patterns of astrocyte differentiation and activity in the MNTB; and 3) To determine the relationship between maternal care, auditory development and MNTB auditory map activity. Altogether, these studies will determine the contribution of glial cells to the maturation of central auditory circuits in mammals, and increase our understanding of how experience and intrinsic programs interact to generate developmental plasticity in the auditory system. Auditory impairments such as deafness are caused by defects in different cellular and molecular components of the ear. However, recent evidence suggests that central nervous system malfunction in the auditory system contributes to neuropsychiatric diseases and other forms of neurologic disease with a developmental onset. The work in this proposal will define how patterns of activity in brain auditory maps change during development, providing clues to understand how these patterns may be affected in disease conditions such as autism and schizophrenia.