Neurons and Circuits of Periloivary Nuclei

描述（由申请人提供）：下丘（IC）是中枢听觉系统几乎所有上行和下行投射整合的主要部位。IC神经元的一些基本生理反应特性受到其抑制性输入的深刻影响。对IC的一些抑制起源于局部，但对IC的显著抑制性输入来自上级橄榄复合体和背侧（DNLL）和腹侧（VNLL）丘系核。 本研究计划的长期目标是揭示中枢听觉抑制回路的细胞机制。本申请的目的是阐明上级旁橄榄核（SPON）在听觉中的功能作用，SPON是支配IC的上级橄榄的一个突出的抑制核。我们的中心假设是，SPON输入的性质，分布和时间调制的VNLL，DNLL和IC的神经元的反应。 第一个具体的目的是揭示拓扑结构的内在和下丘的投射SPON细胞的细胞内标记脑切片。 第二个具体的目标是揭示来自SPON，DNLL和VNLL的抑制IC输入的收敛。为此，将不同的顺行示踪分子注射到这些核的相应频率区域中，将通过光学和电子显微镜进行检查。 第三个目的是确定SPON听觉诱发反应的神经递质基础。将使用单单位细胞外记录技术研究SPON单位对神经递质GABA和甘氨酸的受体拮抗剂的离子电渗应用之前、期间和之后的声音响应。 总的来说，这些结果将提供深入了解机制的整合抑制性突触，可能是推广到其他中枢神经系统电路。这些信息对于技术的进步是必要的，以修复基因异常，受损或退化的大脑部分。

DESCRIPTION (provided by applicant): The inferior colliculus (IC) is a major site of integration of virtually all ascending and descending projections of the central auditory system. Several fundamental physiological response properties of IC neurons are profoundly influenced by their inhibitory inputs. Some of the inhibition to IC originates locally, but significant inhibitory inputs to the IC arises from the superior olivary complex and the dorsal (DNLL) and ventral (VNLL) lemniscal nuclei. The long-term goal of this research program is to reveal cellular mechanisms of central auditory inhibitory circuits. The objective of this application is to clarify the functional role in hearing of the superior paraolivary nucleus (SPON), a prominent inhibitory nucleus of the superior olive that innervates the IC. Our central hypothesis is that the nature, distribution and timing of SPON inputs modulates responses of neurons in the VNLL, the DNLL and the IC. The first specific aim is to reveal the topography of intrinsic and sub-collicular projections of SPON by intracellular labeling of SPON cells in brain slices. The second specific aim is to uncover the convergence of inhibitory IC inputs originating from SPON, DNLL and VNLL. To do so, injections of distinct anterograde tracer molecules into the corresponding frequency regions of these nuclei will be examined by light and electron microscopy. The third aim is to determine the neurotransmitter basis of auditory evoked responses in SPON. Single-unit extracellular recording techniques will be used to study responses of SPON units to sounds before, during and after the iontophoretic application of receptor antagonists for the neurotransmitters GABA and glycine. Collectively, the results will provide insight into mechanisms of integration of inhibitory synapses that may be generalizable to other CNS circuits. Such information is necessary for advancements in technologies to repair genetically abnormal, damaged or degenerating parts of the brain .