Functional Approach to Communication Sound Processing in Mouse Auditory Cortex

描述（由申请人提供）：对通信声音处理的神经基础的听觉研究通常没有考虑通信自然发生的社会背景。因此，听觉系统如何能够检测，区分和分类通信呼叫，尽管自然扬声器的变化是知之甚少，因为是社会互动影响这种处理的机制。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，从而推断自然沟通过程中的潜在缺陷。我们在超声波通信的小鼠模型中追求这一点，其中两类呼叫（由小鼠幼仔和成年雄性发出的呼叫）具有不同的含义，并且可以对雌性具有不同程度的行为相关性。这里的目标是揭示这些呼叫类别的表示是如何通过从初级到高阶听觉皮层领域的分层处理来转变的，以及不同的自然社会经验如何与呼叫产生编码变化。我们的中心假设是，转换细化呼叫编码，以促进沟通任务，社会经验和神经化学系统修改这种神经转化行为相关性的收购。这项研究的基本原理是，一旦我们知道听觉皮层中的神经可塑性塑造行为相关呼叫编码的方式，我们将能够利用小鼠模型的转基因优势来剖析实现这些变化的详细机制。使用清醒小鼠的细胞外电生理学，我们将测试我们的假设与三个具体目标。首先，我们将通过记录识别幼崽（母亲）叫声重要性的动物来确定神经转换通常如何发挥作用，以改进行为相关叫声的编码。其次，我们将通过记录帮助照顾幼崽的处女雌性（共同照顾者）来确定与幼崽的社会经验如何改变这种神经转化。第三，我们将确定一个关键的社会神经化学物质涉及幼犬的呼叫识别，雌激素，与幼犬护理经验，修改神经转化的记录从神经操纵的共同照顾者。该提议的意义在于其独特的能力，即在动物模型中弥合感觉和社会/行为神经科学之间的科学差距，在这种动物模型中，我们可以从系统到分子水平对高级听觉功能（通信）进行进一步研究。 公共卫生相关性：这项研究将使我们能够发现机制的基础上的处理流之间的初级和高阶听觉皮层领域的物种特异性通信的背景下的自然运作。通过阐明这个系统的正常运作，我们的研究结果将是重要的，在暗示方面的沟通编码和可塑性，可能会失败的听觉处理障碍，社会障碍与听觉功能障碍，听力损失和颞叶中风。

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.