Parallel Auditory Pathways in the Brain Stem

描述（由申请人提供）：拟议研究的总体目标是了解哺乳动物听觉中脑、下丘（IC）的功能如何与行为相关。 IC 整合了来自下脑干多个听觉中心、来自相反 IC 和听觉皮层的非上行听觉输入以及来自运动相关结构的信息。这种集成是选择行为相关声音的第一步。非上行听觉输入可以调节 IC 神经元的声音诱发反应，甚至产生专门的反应特性。尽管所有来源的输入都有一定程度的重叠，但它们的终端密度梯度存在差异，这可能会产生功能梯度。我们提出了三个具体目标，每个目标都旨在测试 与将各种听觉和运动输入集成到 IC 相关的广泛假设。 假设 1：IC 神经元的响应特性由沿背腹梯度不同来源的输入比率决定。具体目标 1：我们将使用声音诱发反应的细胞外和细胞内记录来检查行为相关声音参数的选择性、一般反应特性、输入模式的梯度和免疫细胞化学标记之间的关系。 假设 2：至少一些 IC 神经元的声音诱发反应是由非上行通路的输入调节或产生的。具体目标 2：为了评估这些输入对听觉处理的贡献，我们将记录相对 IC 或听觉皮层的可逆失活或电刺激之前、期间和之后 IC 神经元的声音诱发反应。 假设 3：IC 中的感觉处理受到电机相关输入的调节。具体目标3：我们将追踪黑质和苍白球对IC的投射，确定输入是兴奋性的还是抑制性的，并记录黑质可逆失活之前、期间和之后IC神经元的声音诱发反应。 这些实验的结果很可能广泛适用于哺乳动物的听力。所有哺乳动物似乎在 IC 中都有相似的输入梯度以及来自运动通路的输入。了解不同来源的信息如何整合到 IC 中最终可能会对中枢听力和语言障碍的诊断和治疗产生影响。

DESCRIPTION (provided by applicant): The general goal of the proposed research is to understand how the function of the mammalian auditory midbrain, inferior colliculus (IC), relates to behavior. The IC integrates information from multiple auditory centers in the lower brainstem, from non-ascending auditory inputs from the opposite IC and auditory cortex and from motor-related structures. This integration is a first step in selecting for behaviorally relevant sounds. The non-ascending auditory inputs may modulate the sound-evoked responses of IC neurons, or even create specialized response properties. Although the inputs from all sources overlap to some degree, there are differences in their gradients of terminal density, which probably create functional gradients. We propose three specific aims, each designed to test a broad hypothesis related to the integration of the various auditory and motor inputs to the IC. Hypothesis 1: Response properties of IC neurons are determined by the ratios of input from different sources along a dorsoventral gradient. Specific Aim 1: We will use extracellular and intracellular recording of sound-evoked responses to examine the relation between selectivity for behaviorally relevant sound parameters, general response properties, gradients in input patterns, and immunocytochemical markers. Hypothesis 2: Sound-evoked responses of at least some IC neurons are modulated or created by input from non-ascending pathways. Specific Aim 2: To evaluate the contribution of these inputs to auditory processing, we will record sound-evoked responses of IC neurons before, during, and after reversible inactivation or electrical stimulation of the opposite IC or auditory cortex. Hypothesis 3: Sensory processing in the IC is modulated by motor-related inputs. Specific Aim 3: We will trace the projections of substantia nigra and globus pallidus to the IC, determine whether the inputs are excitatory or inhibitory, and record sound-evoked responses of IC neurons before, during and after reversible inactivation of substantia nigra. It is likely that the results of these experiments will be widely applicable to mammalian hearing. All mammals appear to have similar input gradients in the IC as well as inputs from motor pathways. Understanding how information from different sources is integrated in the IC could ultimately have implications for diagnosis and treatment of central hearing and language disorders.