Neurons and Circuits of Periloivary Nuclei

描述(申请人提供)：下丘(IC)是中央听觉系统几乎所有上升和下降投射的主要整合部位。IC神经元的一些基本生理反应特性受到其抑制输入的深刻影响。对IC的部分抑制来自局部，但对IC的重要抑制输入来自上橄榄复合体和背侧(DNLL)和腹侧(VNLL)丘脑核群。 该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。这项应用的目的是阐明上橄榄旁核(SPON)在听力中的功能作用，SPON是支配IC的上橄榄核的一个突出的抑制性核。我们的中心假设是，SPON输入的性质、分布和时机调节了VNLL、DNLL和IC中神经元的反应。 第一个特定的目的是通过脑片中Spon细胞的细胞内标记来揭示Spon的内在和下丘投射的地形图。 第二个具体目标是揭示源自SPON、DNLL和VNLL的抑制性IC输入的收敛。为了做到这一点，将通过光学和电子显微镜检查将不同的顺行示踪剂分子注入这些核的相应频率区域。 第三个目的是确定Spon听觉诱发反应的神经递质基础。单单位细胞外记录技术将被用来研究SPON单位在神经递质GABA和甘氨酸的受体拮抗剂离子导入应用之前、期间和之后对声音的反应。 总而言之，这些结果将提供对抑制性突触整合机制的洞察，这些机制可能可以推广到其他中枢神经系统回路。这些信息对于修复大脑基因异常、受损或退化部分的技术进步是必要的。

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 .