The function of the commissure of the inferior colliculus in auditory processing

耳朵对声音做出反应时产生的神经信号进入脑干两侧的两个镜像通路。虽然左右分区都接收来自双耳的输入，但右侧由关于收听者左侧的声音的信息主导，反之亦然。本申请提出，声源的定位和识别取决于一侧的活动与另一侧进行比较和参考。这种相互作用克服了一侧神经元的输出是模糊的问题，因为它们并不只对声音的一个属性做出反应，因此神经元放电的变化可以反映声音响度的变化，位置的变化，或两者兼而有之。我们认为，连接两个下丘（中脑的听觉中心，脑干通路的顶点）的大束纤维提供了介导这种左右比较的基础。由于所有到达高级皮质中枢的信号都是在下丘内处理的，因此下丘的位置非常适合促进这种相互作用。此外，连接一个下丘与另一个下丘的纤维束（连合）是每个下丘接收的最大输入之一，它以高度组织化的方式终止于下丘内。我们试图通过暂时停用一侧大脑的下丘来研究连合连接的功能作用，并研究这对另一侧下丘对声音的神经反应有什么影响。我们已经开发并测试了一种通过冷却来快速灭活丘的方法，这是通过在丘表面放置一小圈不锈钢管来实现的，我们通过它泵入零度以下的冷却剂。我们可以通过用一个微小的热电偶测量大脑温度来检查冷却效果是否仅限于预期的结构，但作为双重检查，我们还将采用一种方法，使我们能够将阻止神经活动的药物注入下丘。我们还将检查直接切断连合纤维的效果。实验将在麻醉的豚鼠中进行，这样我们就可以记录声音引起的神经活动。我们将测量大脑活动的不同方面，包括单个神经元的反应（在下丘的不同区域同时记录），以及代表大量神经元活动的电信号。通过比较其他下丘失活之前、期间和之后对不同类型和组合的声音刺激的这些细颗粒和概括反应，我们将发现一个下丘在不同情况下如何影响另一个下丘。我们预测，阻塞连合输入将影响声音处理的几个方面-试点研究支持的观点。具体来说，我们希望观察到对声音特征的反应变化，这些特征表明了它的位置。不同位置的声音会引起耳朵之间声音的水平和时间的差异。关于大脑如何根据这些差异计算声音位置的最新发现表明，左右活动的参照很重要。我们对下丘连合的组织结构知之甚少，对它在听觉中的功能更是知之甚少。因此，这项研究的结果将提供有关这些连接在听觉中的作用的重要信息，并帮助我们更好地理解声音感知的机制。下丘也正在被评估用于植入听觉-大脑假体，以使那些因创伤或疾病而失去耳朵和大脑之间神经的患者受益。成功开发这样一种装置取决于对下丘的更深入了解。

Neural signals generated by the ears in response to sounds feed into two mirror image pathways on either side of the brainstem. While both left and right divisions receive inputs from both ears, the right side is dominated by information about sounds on the listener's left side and vice versa. This application proposes that the localisation and recognition of sound sources depend on the activity in one side being compared and referenced to the other. This interaction overcomes the problem that the outputs of neurons on one side alone are ambiguous because they don't respond exclusively to one attribute of sound, thus a change in a neuron's firing can reflect a change in the loudness of a sound, a shift in its position, or both. We propose that the large bundle of fibres interconnecting the two inferior colliculi (the auditory centres in the midbrain where the brainstem pathways culminate) provides the basis for mediating this left- right comparison. Since all signals reaching the higher cortical centres are processed en route within the inferior colliculi they are ideally situated to facilitate such an interaction. Furthermore, the bundle of fibres (the commissure) that connects one colliculus to the other is one of the largest inputs each inferior colliculus receives, and it terminates within the colliculus in a highly organised fashion. We seek to investigate the functional role of the commissural connections by temporally deactivating the inferior colliculus on one side of the brain and investigating what effect this has on the neural responses to sounds in the other inferior colliculus. We have developed and tested a means of rapidly deactivating the colliculus by cooling it. This is achieved by placing a small loop of stainless steel tubing on its surface through which we pump a coolant at subzero temperature. We can check that that the cooling effect is limited to the intended structure by measuring brain temperature with a tiny thermocouple, but as a double check, will also apply a method that enables us to infuse drugs that block neural activity into the inferior colliculus. We will also examine the effect of cutting the commissural fibres directly. The experiments will be performed in the anaesthetised guinea pig so that we can record the neural activity elicited by sounds. We will measure different aspects of brain activity, including the responses of single neurons (recorded simultaneously in different regions of the inferior colliculus), and electrical signals that represent the activity of large populations of neurons. By comparing these fine grain and summary responses to different types and combinations of sound stimuli before, during, and after deactivation of the other inferior colliculus we will discover how one inferior colliculus influences the other in different situations. We predict, that blocking commissural input will influence several facets of sound processing - a view supported by pilot studies. Specifically, we expect to observe changes in responses to features of sound that signal its location. Sounds in different locations give rise to differences in the level and timing of the sound between the ears. Recent discoveries about how the brain computes sound position from these differences suggest that referencing of left and right activity is important.We know little about the organisation of commissure of the inferior colliculus, and even less about its function in hearing. The outcomes of this research will, therefore, provide information of fundamental importance about the role of these connections in hearing, and help us better to understand the mechanisms of sound perception. The inferior colliculus is also being assessed for implanting an auditory- brain prosthesis to benefit patients who, through trauma or disease, have lost the nerves between the ears and the brain. Success in developing such a device depends on a greater understanding of the inferior colliculus.