Synaptic Organization of the Auditory System

描述（由申请人提供）：下丘（IC）是一个中脑结构，几乎所有上升的听觉信息都在通往听觉皮层的途中终止。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)采用生理学和神经解剖学方法在完整动物身上进行的实验将表明，IC中含有神经元的反应特性与脑干输入直接相关的功能区。使用轴突标记的实验将表明，主要的抑制性输入在不同的功能区终止。使用逆行细胞标记的实验将显示IC的哪些输入与具有不同双耳和单耳反应特性的神经元相关。(2)完整动物实验将研究IC功能区的输出，并可能暗示IC参与两种不同类型的高级听觉处理通路：传递声音位置信息的双耳通路和传递复杂声音频谱特性信息的单耳通路。(3)在IC的脑切片制备实验中，将研究由独特放电模式和特定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。实验将确定不同的突触反应是由于突触输入（由配体门控的突触后受体介导）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（通过刺激外侧小网膜引起）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)脑切片制备的实验将在形态学、分子和递质水平上研究结构-功能关系。这些实验将从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和递质含量的表达。(5)最后，在完整动物身上进行的实验将使用细胞内记录，以便与大脑切片进行直接比较。我们将了解是否在成年动物中发现IC细胞类型，以及细胞内反应如何与外侧小网膜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.