Functional Approach to Communication Sound Processing in Mouse Auditory Cortex

描述(由申请人提供)：对交流声音处理的神经基础的听觉研究通常没有考虑到自然发生交流的社会背景。因此，听觉系统如何能够检测、区分和分类交流呼叫，尽管自然的说话人可变性，以及社会互动影响这一处理的机制，人们还知之甚少。我们的长期目标是揭示听觉系统编码社会获得性发声的电路、细胞和分子机制，以便可以推断自然交流处理的潜在缺陷。我们在一个超声波交流的小鼠模型中探索这一点，其中两种类别的叫声(由小鼠幼崽发出的叫声和由成年雄性发出的叫声)具有不同的含义，并且可能与雌性具有不同的行为相关性。这里的目的是揭示这些呼叫类别的表征是如何通过分层处理从初级听觉皮层区域转换到更高阶听觉皮层区域的，以及不同的自然社会体验如何产生编码变化。我们的中心假设是，这种转换改进了呼叫编码，以促进交流任务，并且随着行为相关性的获得，社会经验和神经化学系统修改了这种神经转换。这项研究的基本原理是，一旦我们知道了听觉皮质中神经可塑性塑造行为相关呼叫编码的方式，我们就能够利用小鼠模型的转基因优势来剖析使这些变化发生的详细机制。利用清醒小鼠的细胞外电生理学，我们将以三个具体目标来验证我们的假设。首先，我们将通过记录认识到幼崽叫声重要性的动物(母亲)的声音，来确定神经转换是如何正常工作的，以完善与行为相关的叫声的编码。其次，我们将通过记录帮助照顾幼崽的处女雌性幼崽的记录，确定与幼崽的社会经验如何改变这种神经转换。第三，我们将确定在幼崽叫声识别中涉及的一种关键的社会神经化学物质--雌激素，如何与幼崽护理经验一起通过记录来自激素操纵的协护者的记录来修改神经转换。这一建议的意义在于，它具有独特的能力，可以在动物模型中弥合感觉和社会/行为神经科学之间的科学鸿沟，在动物模型中，我们可以进一步研究从系统到分子水平的高级听觉功能(沟通)。 公共卫生相关性：这项研究将使我们能够发现在物种特定交流的背景下，初级和更高阶听皮层区域之间的处理流自然功能的潜在机制。通过阐明该系统的正常运行，我们的结果将在通信编码和可塑性方面具有重要意义，这些方面可能在听觉加工障碍、伴有听觉功能障碍的社会障碍、听力损失和颞叶中风中失效。

DESCRIPTION (provided by applicant): Auditory research into the neural basis of communication sound processing has generally been conducted without accounting for the social contexts in which communication naturally occurs. Hence, how the auditory system is able detect, discriminate and categorize communication calls despite natural speaker variability is poorly understood, as are the mechanisms by which social interactions affect this processing. Our long-term goal is to uncover the circuit, cellular and molecular mechanisms underlying the auditory system's encoding of socially-acquired vocalizations, so that causes underlying deficits in natural communication processing can be inferred. We pursue this in a mouse model of ultrasound communication wherein two categories of calls (those emitted by mouse pups and by adult males) carry different meanings and can have different levels of behavioral relevance to a female. The objective here is to uncover how the representation of these call categories is transformed by hierarchical processing from a primary to a higher-order auditory cortical field, and how different natural social experiences with the calls produce coding changes. Our central hypothesis is that the transformation refines call coding to facilitate communication tasks, and that social experience and neurochemical systems modify this neural transformation as behavioral relevance is acquired. The rationale for this research is that once we know the manner by which neural plasticity in auditory cortex shapes the coding of behaviorally relevant calls, we will be able to exploit the transgenic advantages of the mouse model to dissect the detailed mechanisms enabling these changes. Using extracellular electrophysiology in awake mice, we will test our hypothesis with three specific aims. First, we will determine how the neural transformation normally functions to refine the encoding of behaviorally relevant calls by recording from animals that recognize the significance of pup calls (mothers). Second, we will determine how social experience with pups modifies this neural transformation by recording from virgin females that help care for pups (co-carers). Third, we will determine how a key social neurochemical implicated in pup call recognition, estrogen, works with pup care experience to modify the neural transformation by recording from hormonally manipulated co-carers. This proposal's significance lies in its unique ability to bridge the scientific gap between sensory and social/behavioral neuroscience in an animal model in which we can pursue future studies of a high level auditory function (communication) from a system down to a molecular level. PUBLIC HEALTH RELEVANCE: This research will enable us to discover mechanisms underlying the natural functioning of the processing stream between a primary and higher-order auditory cortical field in the context of species-specific communication. By elucidating the normal operation of this system, our results will be important in implicating aspects of communication coding and plasticity that may fail in auditory processing disorders, social disorders with auditory dysfunctions, hearing loss and temporal lobe strokes.