Functional interrogation of the mouse somatosensory thalamic interneuron in sensory perception and rhythmic states

小鼠体感丘脑中间神经元在感觉知觉和节律状态下的功能询问

• 批准号: 10685957
• 负责人: Jane Yi
• 金额: $ 7.6万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10685957
• 关键词: 3-Dimensional; Address; Amplifiers; Arithmetic; Arousal; Attention; BRAIN initiative; Behavior; Behavioral; Biophysical Process; Brain; Brain imaging; Brain region; Calcium; Cannulas; Cell Nucleus; Cell physiology; Cells; Cellular Structures; Code; Communication; Complex; Computer Models; Computer Simulation; Data; Data Set; Dendrites; Detection; Development; Disease; Distal; Electroencephalography; Electrophysiology (science); Endowment; Evaluation; Fellowship; Generations; Genetic Complementation Test; Glutamates; Goals; Home; Image; In Vitro; Individual; Interneurons; Location; Mammals; Medial lemniscus; Mediating; Modeling; Mus; Neurobiology; Neurons; Optics; Output; Pathologic; Pattern; Perception; Periodicity; Physiological; Play; Population; Positioning Attribute; Preparation; Process; Property; Rodent; Role; Seizures; Sensory; Shapes; Signal Transduction; Sleep; Slice; Source; Speed; Structure; Surface; Synapses; Synaptic Vesicles; Techniques; Testing; Thalamic Nuclei; Thalamic structure; Time; Training; Trees; Universities; Validation; Vibrissae; Work; career development; cell type; computational neuroscience; data-driven model; experimental study; in vivo; in vivo imaging; insight; instrument; interest; member; millisecond; mind control; multi-electrode arrays; multi-photon; multiphoton imaging; neural; neural circuit; neuronal cell body; next generation; novel; operation; optogenetics; receptive field; reconstruction; response; sensory input; somatosensory; targeted treatment; temporal measurement; tool; two-photon; vesicular release; voltage

ABSTRACT/SUMMARY The mouse somatosensory thalamus participates in fundamental processes including sensory processing, sleep and pathological rhythmic behaviors like seizure. Local thalamic interneurons have been considerably overlooked due to their sparsity in the total neuronal population. However, their extensive dendritic arborizations spanning almost the entire breadth of the nucleus, together with my preliminary data, point to an important role for these cells in thalamic functions. Thalamic interneuron dendrites are capable of releasing synaptic vesicles, defying traditional definitions of neuronal input and output structures, while greatly increasing their capacity for complex computations. Of interest, local thalamic interneurons are also capable of forming diverse and uncommon synaptic relationships including triadic synapses. The primary conceptual goals this project seeks to address are to define the rules that govern dendritic signal integration and to define the functional role these interneurons play in the canonical thalamocortical circuit. I hypothesize that unique structural features enable unique functions. Specifically, I predict that electrotonically isolated dendritic locations enable numerous encoding processes to occur simultaneously and independently from the soma. Thus, thalamic interneurons pose unique opportunities to study fundamental principles of neuronal computation including the ambiguous role of triadic inhibition. Taking place at Columbia University with Sponsor Prof. Chris Makinson and Co-Sponsor Prof. Liam Paninksi, I will use the newest generation of high-gain voltage indicators and multi-photon in vitro and in vivo imaging to investigate the imperative questions outlined above. This fellowship represents a substantial opportunity for high-quality training in state-of-the-art imaging and computational neuroscience techniques and approaches that complement my background in neurobiology and electrophysiology. I aim to address the influence of local interneurons in thalamic functions by observing and manipulating their activity during thalamic oscillations. I will also apply synthetic synaptic inputs to probe with precision input distribution patterns and the biophysical mechanisms underlying dendritic integration in thalamic interneurons. Data from these experiments will be used to build realistic and well constrained computer simulations to further test precise mechanisms in shaping receptive field structures. I expect to find that interneurons act as an integral member of the thalamocortical circuit and to gain insight into fundamental concepts of neuronal computation through their interrogation. Moving forward, I hope to build upon the conceptual and technical advances outlined here to uncover the causative mechanisms involved in sensory perception and the role of thalamic interneurons in disease.

摘要/摘要 小鼠的体感丘脑参与基本的过程，包括感觉处理、睡眠 以及像癫痫这样的病理性节律行为。局部丘脑中间神经元在很大程度上 由于它们在神经元总数中的稀疏性而被忽视。然而，它们广泛的树枝状树枝 跨越几乎整个原子核的宽度，加上我的初步数据，表明了一个重要的作用 这些细胞在丘脑中的功能。丘脑间神经元树突能够释放突触小泡， 挑战神经元输入和输出结构的传统定义，同时极大地提高其能力 复杂的计算。有趣的是，局部丘脑中间神经元也能够形成不同的和 罕见的突触关系，包括三叉神经突触。这个项目寻求的主要概念目标是 目的是定义管理树突状信号整合的规则，并定义这些功能角色 中间神经元在典型的丘脑皮质环路中发挥作用。我假设独特的结构特征使 独一无二的功能。具体地说，我预测，电子隔离的树突位置能够使许多 编码过程独立于胞体同时进行。因此，丘脑中间神经元 提供独特的机会学习神经元计算的基本原理，包括模糊的角色 三叉戟的抑制。在哥伦比亚大学举行，赞助商克里斯·梅金森教授和共同赞助商 Liam Paninksi教授，我将在体外使用最新一代的高增益电压指示器和多光子 活体成像，以研究上述迫切需要的问题。这一奖学金代表着一个重要的 在最先进的成像和计算神经科学技术和 这些方法补充了我在神经生物学和电生理学方面的背景。我的目标是解决 局部中间神经元在丘脑中的活动观察和调控对丘脑功能的影响 震荡。我还将应用合成突触输入来探测精确的输入分布模式和 丘脑中间神经元树突整合的生物物理机制。来自这些实验的数据 将用于构建逼真且约束良好的计算机模拟，以进一步测试 塑造感受野结构。我希望发现，中间神经元是 丘脑皮质回路，并通过其 审问。展望未来，我希望在这里概述的概念和技术进展的基础上， 揭示感觉知觉的致病机制和丘脑中间神经元在脑损伤中的作用 疾病。