Functional modularity and multisensory convergence in the lateral cortex of the mouse inferior colliculus

项目摘要 携带躯体感觉信息的投射会聚在听觉内的几个核团上 系统。虽然这些连接的确切功能尚不清楚，但它们可以贡献和修改 耳鸣患者存在病理性声音知觉。尽管目前的治疗方法试图利用这些 改善耳鸣症状的途径，对它们的解剖学和生理学知之甚少。这个 下丘的外侧皮质是这样一种听觉结构，它接受来自两者的大量输入 脑干和皮质体感核团。尽管这种结构长期以来被认为与多种感官有关 整合，输入到外侧皮质的终止模式被分成不同的流： 躯体感觉输入靶区的高密度GAD67染色，称为模块，而听觉 输入终止于模块外区域。鉴于功能和解剖数据之间的这种不匹配，目标是 这一建议的目的是揭示大脑外侧区多感官会聚的回路和机制。 大脑皮层。将探索两个主要假设：1)外侧模块区域和模块外区域内的细胞 大脑皮层相互沟通，潜在地产生多突触多感觉融合，以及2) 模块或模块外区域中的单个细胞的树突延伸到互补区域，因此 同时接受听觉和躯体感觉输入。这些假说将在来自 GAD67-GFP鼠标，在蓝光下可以看到模块。模块化和外模块化单元格 外侧皮质的区域将被记录在整个结构中，并记录潜在的突触前伙伴 将用笼中谷氨酸的激光光刺激来刺激。抑制性和兴奋性输入映射将 构造为确定给定单元格的输入是来自模块化区域、模块外区域还是两者兼而有之。 模块和模块外区域的单元之间的通信程度将被量化。为了进一步 探索模块化和模块化外区域之间的功能差异，自发的量 将确定对这两个区域细胞的抑制性和兴奋性输入。以确定单个细胞是否 整合体感和听觉信息，来自背柱的体感投射 细胞核将预先标记红移的视蛋白C1V1。这条路径将被绿色激光刺激， 从下丘中央核发出的听觉通路将通过激光去刺激术得到刺激。 用紫外光激光器。将检查每条通路的突触特性；如果细胞对两种刺激都有反应 发现，刺激间间隔将被系统地改变，以确定时机对 双峰响应。上面概述的实验将进一步表征躯体感觉输入和 外侧皮质的内在回路，这可能对正常和病理都有重要意义 听证。此外，这些实验可能揭示关于整合的一般性原则 在单个细胞水平上的多感觉输入。

Project Summary Projections carrying somatosensory information converge upon several nuclei within the auditory system. While the exact function of these connections is unknown, they can contribute to and modify the pathological sound percepts present in tinnitus patients. Though current treatments attempt to exploit these pathways to ameliorate tinnitus symptoms, very little is known about the their anatomy and physiology. The lateral cortex of the inferior colliculus is one such auditory structure that receives heavy input from both brainstem and cortical somatosensory nuclei. Though this structure has long been implicated in multisensory integration, the termination patterns of inputs to the lateral cortex are segregated into distinct streams: the somatosensory inputs target areas of high-density GAD67 staining, known as modules, while the auditory inputs terminate in extramodular areas. Given this mismatch between functional and anatomical data, the goal of this proposal is to reveal the circuitry and mechanisms underlying multisensory convergence in the lateral cortex. Two main hypotheses will be explored: 1) cells within modular and extramodular regions of the lateral cortex communicate with one another, potentially producing multisynaptic multisensory convergence, and 2) the dendrites of individual cells in modular or extramodular regions extend into the complementary region, thus receiving both auditory and somatosensory input. These hypotheses will be tested in brain slices from the GAD67-GFP mouse, in which modules can be visualized under blue light. Cells in modular and extramodular regions of the lateral cortex will be recorded from and potential presynaptic partners throughout the structure will be stimulated using laser photostimulation of caged glutamate. Inhibitory and excitatory input maps will be constructed to determine whether inputs for a given cell arise from modular areas, extramodular areas, or both. The degree of communication between cells in modular and extramodular areas will be quantified. To further explore the functional differences between modular and extramodular areas, the amount of spontaneous inhibitory and excitatory input to cells in both regions will be determined. To ascertain whether individual cells integrate both somatosensory and auditory information, somatosensory projections from the dorsal column nuclei will be pre-labeled with a red-shifted opsin, C1V1. This pathway will be stimulated with a green laser, and the auditory pathway from the central nucleus of the inferior colliculus will be stimulated via laser uncaging with a UV laser. The synaptic properties of each pathway will be examined; if cells responding to both stimuli are found, the interstimulus interval will be systematically altered to determine the effect of timing on the bimodal response. The experiments outlined above will further characterize the somatosensory inputs and intrinsic circuitry of the lateral cortex, which could have important implications for both normal and pathological hearing. Furthermore, these experiments may reveal generalizable principles regarding integration of multisensory inputs at the level of a single cell.