Synaptic Organization of the Auditory System

描述（由申请人提供）：下丘（IC）是一个中脑结构，几乎所有上行听觉信息都在到达听觉皮层的路径中终止。我们的最终目标是了解IC中声音处理的细胞机制。本研究项目将采用多种实验方法。(1)使用生理学和神经解剖学方法在完整动物中进行的实验将表明，IC包含功能区，其中神经元的响应特性与脑干输入直接相关。使用轴突标记的实验将表明，IC的主要抑制性输入终止于单独的功能区。使用逆行细胞标记的实验将显示哪些输入到IC与具有不同双耳和单耳响应特性的神经元相关。(2)在完整的动物实验将研究IC的功能区的输出，并可能牵连IC的途径，导致两种不同类型的更高层次的听觉处理：双耳通路传达有关声音位置的信息，和单声道通路，传达有关复杂声音的频谱特性的信息。(3)IC的脑切片制备实验将研究由独特的放电模式和特定的钾电流定义的神经元类型。这些细胞类型的突触反应也不同。这些实验将确定不同的突触反应是由于突触输入（由配体门控突触后受体介导）还是由于膜特性（与电压激活的离子通道有关）。将检查对突触输入（通过刺激外侧丘系诱发）和人工突触输入（模拟突触电流而不激活突触后受体）的反应。(4)在脑切片制备实验将调查在形态，分子和发射器水平的结构功能关系。这些实验将在形态学上标记功能细胞类型，然后测试它们的离子通道亚基表达和递质含量。(5)最后，在完整动物中的实验将使用细胞内记录，以便与大脑切片直接比较。我们将了解IC细胞类型是否存在于成年动物中，以及细胞内反应如何与外侧丘系的电刺激以及单耳和双耳声音的刺激相关。

DESCRIPTION (provided by applicant): The inferior colliculus (IC) is a midbrain structure where virtually all ascending auditory information terminates in route to the auditory cortex. Our ultimate objective is to understand the cellular mechanisms that underlie sound processing in the IC. This research project will employ a diverse set of experimental approaches. (1) Experiments in the intact animal using physiological and neuroanatomical methods will show that the IC contains functional zones where the response properties of the neurons are directly related to the brainstem inputs. Experiments using axonal labels will show that major inhibitory inputs to the IC terminate in separate functional zones. Experiments using retrograde cell markers will show which inputs to the IC are related to neurons with different binaural and monaural response properties. (2) Experiments in the intact animal will study the outputs of the functional zones in the IC and may implicate the IC in pathways that lead to two different types of higher-level auditory processing: a binaural pathway conveying information about sound location, and a monaural pathway that conveys information about the spectral properties of complex sounds. (3) Experiments in a brain slice preparation of the IC will investigate neuron types defined by unique discharge patterns and specific potassium currents. These cell types also differ in their synaptic responses. The experiments will determine if the different synaptic responses are due to the synaptic inputs (mediated by ligand-gated postsynaptic receptors) or to the membrane properties (related to voltage-activated ion channels). Responses will be examined to synaptic inputs (evoked by stimulation of the lateral lemniscus) and to artificial synaptic inputs (that simulate the synaptic currents without activating the postsynaptic receptors). (4) Experiments in a brain slice preparation will investigate structure-function relationships at the morphological, molecular, and transmitter level. These experiments will morphologically label functional cell types and then test them for expression of ion channel subunits and transmitter content. (5) Finally, experiments in the intact animal will use intracellular recording to allow direct comparisons to the brain slice. We will learn whether the IC cell types are found in the adult animal, and how the intracellular responses are related to electrical stimulation of the lateral lemniscus and stimulation by monaural and binaural sounds.