How does auditory experience shape neural sensitivity to acoustic events? Non-invasive investigations in animal models.

探测环境变化并迅速做出反应的能力，例如物体的出现、消失或移动，对生存有重大影响。检测声学环境的变化对这一过程至关重要；我们经常在黑暗或视觉混乱的环境中依靠我们的听力，以及发生在视野之外的事件。由于检测声学变化是一种基本而重要的能力，而且现代环境的特点是“噪声污染”或相互竞争的声学信息来源--因此检测混合声音中的重要事件的必要性日益重要。目前的建议试图了解听觉大脑对正在展开的声学环境的敏感性是如何受到先前长期暴露变化的影响的，以及这种敏感性在成年后的变化程度。在评估大脑机制对声学变化的敏感性方面存在固有的困难，这意味着就我们所知，目前的提案中提出的问题从未得到实验解决。造成这一缺陷的原因之一是需要仔细控制发育经历和接触声音模式，这一要求使得在人类受试者中进行研究几乎是不可能的。同样，在动物模型中解决这些问题也受到以下因素的限制：在评估暴露/训练的结果时出现困难，以及缺乏关于电生理记录可能指向的位置(即大脑的哪些区域)的基本知识(或者实际上检测声学变化与单个神经元水平上的活动如何相关)。在这里，我们提出了一种方法，通过在动物模型(小鼠和豚鼠)中进行无创性的、大体的脑活动测量来评估声学变化检测潜在机制的长期可塑性，对于动物模型，行为相关性和发育经验可以仔细控制。为了测量大脑的总体活动，我们将使用一种小型动物脑磁图(MEG)设备。相对于其他测量小动物大脑反应的方法，如脑电(EEG)，这项新兴技术完全是非侵入性的，提高了测量事件相关反应的效率，并促进了对单个动物的重复测量。在提出的第一个实验中，我们将研究成年后的训练对随后的神经变化敏感性的影响。两组动物将被暴露在相同的听觉刺激下，包括两个声音特征(音调和音色)的变化。其中一组将接受训练，以对音调变化做出反应，而忽略音色变化，另一组则相反。对照组将暴露在相同的刺激下，但没有训练元素。然后将记录没有行为的麻醉动物的变化诱发的大脑反应(使用脑磁图测量)，以确定这种训练是否以及以何种方式改变了听觉皮质的变化检测机制。第二个实验将调查在发育过程中被动暴露于声音的程度，塑造成年后变化检测的神经表征。不同的动物群体将被饲养在特定控制的声音环境中，以便跨群体的声音特征的统计将是相同的，但变化的统计(遇到的变化的频率)是不同的。暴露后，将测量脑磁图对声学变化的反应。群体之间反应模式的差异将具体归因于群体对变化模式的不同暴露。这项实验的结果将揭示声学变化的统计数据如何塑造大脑皮层反应，以及哪些变化(罕见或常见)在这一过程中占主导地位。

The ability to detect and respond quickly to changes in the environment, for example, the appearance, disappearance or movement of an object, impacts significantly on survival. Detecting changes in the acoustic environment is critical to this process; we often rely on our hearing in the dark or in visually-cluttered environments, and for events that occur beyond the field of vision. Because detecting acoustic changes is such a basic and vital ability, and since modern environments are characterized by 'noise pollution' or competing sources of acoustic information - the need to detect important events within a mixture of sounds, is increasingly important. The present proposal seeks to understand how the auditory brain's sensitivity to the unfolding acoustic environment is shaped by previous long-term exposure changes, and the degree to which this sensitivity is mutable during adulthood. Inherent difficulties in assessing the nature of brain mechanisms underlying sensitivity to acoustic changes means that the questions posed in the current proposal have never been, to the best of our knowledge, addressed experimentally. One reason for this deficit lies in the need to control carefully developmental experience and exposure to sound patterns, a requirement that renders investigations in human subjects almost impossible. So too, addressing such questions in animal models is limited by the difficulties that arise in evaluating the results of exposure/training, coupled with a lack of basic knowledge concerning the sites (i.e. which brain areas) to which electrophysiological recordings might be directed (or indeed how detecting acoustic changes relates to activity at the level of single neurons). Here, we propose a method of assessing the long term plasticity of mechanisms underlying detection of acoustic changes by means of non-invasive, gross brain activity - measurements in animal models (mice and guinea pigs), for which behavioral relevance and developmental experience can be carefully controlled. To measure gross brain activity we will employ a small animal MEG (magneto-encephalography) device. Relative to other means of measuring brain responses from small animals, such as EEG (electro-encephalography), this emerging technology is entirely non-invasive, increasing the efficiency of measuring event-related responses, and facilitating repeated measurements from individual animals. In the first experiment proposed, we will examine the effects of training in adulthood on subsequent neural sensitivity to change. Two groups of animals will be exposed to an identical auditory stimulus, containing changes in two sound features (pitch and timbre). One group will be trained to respond to pitch changes, while ignoring timbre changes, and vice versa for the other group. A control group will be exposed to the same stimuli but without a training element. Change-evoked brain responses (measured using MEG) will then be recorded from non-behaving anesthetized animals to determine whether, and in which manner, such training alters change-detection mechanisms in auditory cortex, A second experiment will investigate the extent to which passive exposure to sound during development, shapes neural representations of change detection in adulthood. Different groups of animals will be raised in specifically controlled sound environments such that the statistics of sound features across groups will be identical, but the statistics of changes (the frequency of changes encountered) different. Following exposure, MEG responses to acoustic changes will be measured. Differences in response patterns between groups will be specifically attributable to the differential exposure of the groups to patterns of changes. The outcome of this experiment will reveal the means by which statistics of acoustic changes shape cortical responses, and which changes (rare or commonly-occurring) are dominant in this process.