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进行的听觉研究通常没有考虑到交流自然发生的社会环境。因此，听觉系统如何能够在说话者自然变化的情况下检测、区分和分类交流呼叫，以及社会互动影响这种处理的机制，我们知之甚少。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，从而推断出自然交流处理中潜在的缺陷。我们在超声通信的小鼠模型中研究了这一点，其中两类呼叫（小鼠幼崽和成年雄性发出的呼叫）具有不同的含义，并且与雌性具有不同程度的行为相关性。本文的目的是揭示这些呼叫类别的表征是如何通过层次处理从初级到高阶听觉皮层场的转换，以及不同的自然社会呼叫经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，以促进沟通任务，而社会经验和神经化学系统在获得行为相关性时修改了这种神经转换。这项研究的基本原理是，一旦我们知道听觉皮层的神经可塑性如何塑造行为相关呼叫的编码，我们将能够利用小鼠模型的转基因优势来解剖这些变化的详细机制。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，我们将通过记录识别幼崽（母亲）呼叫的重要性的动物，确定神经转换如何正常运作，以完善行为相关呼叫的编码。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换。第三，我们将确定一个关键的社会神经化学涉及幼犬呼叫识别，雌激素，如何与幼犬护理经验一起工作，通过记录从激素操纵的共同照顾者修改神经转换。这一建议的意义在于其独特的能力，在动物模型中弥合了感觉和社会/行为神经科学之间的科学差距，我们可以在这个模型中从系统到分子水平进行高水平听觉功能（交流）的未来研究。

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.