Structural and Functional Measures of Auditory Cortical Development

听觉皮质的正常发育始于在听力开始之前制定的路径的大致蓝图，随后是一段依赖于声音诱发的神经活动的精细化时期。这些过程由大脑具有最大适应能力的时间窗口指导，这段时间被称为正常发育的敏感期。这些时期的时间动态对感觉发育至关重要；然而，尽管几十年来猫一直依赖于这一模型来研究正常和异常知觉，但将结构和功能变化与听觉皮质联系起来的彻底调查尚未在猫身上进行。相反，在视觉皮质观察到的神经可塑性原理被广泛应用于所有发育中的皮质区域，而很少考虑大脑区域之间的显著解剖和功能差异。因此，这项研究计划的长期目标是将经典神经解剖学技术与尖端高场功能成像方法相结合，以发展对听觉皮质发育的详细了解。*我们建议将神经元发育的免疫组织化学标记物和逆行示踪剂与先进的、结构和功能的磁共振成像(MRI)相结合，以检查猫的听觉皮质发育。此外，我们将操控声音诱发活动的开始，以确定结构和功能正常发展的敏感期的时间边界。我们将阐明板层发育的模式，监测感觉皮质之间连通性的变化，并建立整个加工层次中皮质功能开始的发育时间表。我们假设这些方法将揭示结构和功能成熟的时间表，该时间表始于核心听觉皮质(A1和AAF)，并向更高水平的领域进行，并受到听力起始延迟的干扰，导致功能异常。*结合现有的成人数据，拟议的研究结果将建立听觉皮质领域的标准发育模式，并允许在结构成熟阶段和皮质功能开始之间得出相关性。此外，这些数据将提供一个模板，可以将异常发展时期产生的模式与之进行比较。

The normal development of auditory cortex begins with a rough blueprint of pathways laid down prior to hearing onset, and is followed by a period of refinement that depends upon sound-evoked neural activity. These processes are guided by windows of time during which the brain is maximally adaptable, referred to as sensitive periods for normal development. The temporal dynamics of these periods are crucial to sensory development; however a thorough investigation relating structural and functional changes to auditory cortex has not been undertaken in the cat, despite decades of relying upon this model for the study of normal and abnormal perception. Instead, principles of neural plasticity observed in the visual cortex are broadly applied to all developing cortical areas with little consideration for significant anatomical and functional differences between brain regions. Thus, the long-term goal of this research program is to combine classical neuroanatomical techniques with cutting-edge high-field functional imaging methodologies to develop a detailed understanding of auditory cortical development. ****** We propose to combine immunohistochemical markers of neuronal development and retrograde tracers with advanced, structural and functional magnetic resonance imaging (MRI) to examine auditory cortical development in the cat. Moreover, we will manipulate sound-evoked activity onset to define temporal boundaries of sensitive periods for normal development of structure and function. We will elucidate patterns of laminar development, monitor changes in connectivity between sensory cortices, and establish developmental timelines for the onset of cortical function throughout the hierarchy of processing. We hypothesize these methods will reveal a timeline for structural and functional maturity that begins in core auditory cortex (A1 and AAF), and proceeds toward higher-level fields, and which is perturbed by delayed hearing onset, leading to functional abnormalities. ****** In combination with existing adult data, results of the proposed studies will establish normative patterns of development in auditory cortical fields, and allow correlations to be drawn between stages of structural maturity, and the onset of cortical function. Additionally, these data will provide a template against which patterns arising from periods of abnormal development may be compared.********************