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

小鼠下丘外侧皮层的功能模块化和多感觉收敛

• 批准号: 9377490
• 负责人: Alexandria Marie Lesicko
• 金额: $ 3.7万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-15 至 2018-10-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9377490
• 关键词: Acoustic Stimulation; Anatomy; Area; Auditory; Auditory area; Auditory system; Bathing; Brain; Brain Stem; Cell Nucleus; Cells; Communication; Complex; Data; Dendrites; Dependovirus; Development; Environment; Event; Fluorescence; Frequencies; Glutamates; Goals; Hearing; Image; Individual; Inferior Colliculus; Injections; Knowledge; Label; Lasers; Lateral; Light; Location; Maps; Midbrain structure; Modality; Mus; Neurons; Opsin; Pathologic; Pathway interactions; Patients; Pattern; Physiologic pulse; Physiology; Play; Problem Solving; Property; Research; Role; Sensory; Slice; Stains; Stimulus; Stream; Structure; Symptoms; Synapses; System; Testing; Tinnitus; Work; auditory nuclei; auditory pathway; base; density; dorsal column; experimental study; extracellular; extrastriate visual cortex; multimodality; multisensory; neurochemistry; patch clamp; presynaptic; response; segregation; sensory system; somatosensory; sound; voltage clamp

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.

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是未知的，但它们可以促进和修改 耳鸣患者的病理性声音感觉。虽然目前的治疗试图利用这些 耳鸣的症状有哪些？耳鸣的症状有哪些？的 下丘的外侧皮层就是这样一个听觉结构，它接受来自两个神经元的大量输入。 脑干和皮层躯体感觉核。尽管这种结构长期以来被认为是多感官的 整合，输入到外侧皮层的终止模式被分成不同的流： 躯体感觉输入靶向高密度GAD 67染色的区域，称为模块，而听觉输入靶向高密度GAD 67染色的区域，称为模块。 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， 这一建议的目的是揭示多感觉会聚在外侧的电路和机制， 皮层两个主要的假设将被探讨：1）细胞模块和模块外区域的外侧 皮质相互沟通，可能产生多突触多感觉会聚，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中， 接受听觉和躯体感觉的输入。这些假设将在来自美国的脑切片中进行测试。 GAD 67-GFP小鼠，其中模块可以在蓝光下可视化。模块化和模块外的单元 侧皮层的区域将被记录从整个结构的潜在突触前伙伴 将使用笼状谷氨酸的激光光刺激来刺激。抑制性和兴奋性输入图将被 被构造为确定给定单元的输入是否来自模块化区域、模块外区域或两者。 将量化模块化和模块外区域中细胞之间的通信程度。进一步 探讨模块和模块外区域之间的功能差异，自发活动的数量， 将确定对两个区域中细胞的抑制性和兴奋性输入。为了确定单个细胞是否 整合躯体感觉和听觉信息，来自背柱的躯体感觉投射 细胞核将用红移视蛋白C1V1预标记。这条通路将被绿色激光刺激， 通过激光撑开刺激下丘中央核的听觉通路 用紫外线激光每个通路的突触特性将被检查;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，以确定时间对刺激的影响 双峰反应。上述实验将进一步表征体感输入， 外侧皮质的内在回路，这可能对正常和病理的 听证会此外，这些实验可以揭示关于整合的可推广的原则， 在单细胞水平上的多感官输入。