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/总结 小鼠躯体感觉丘脑参与感觉加工、睡眠等基本过程 以及癫痫发作等病理性节律行为。局部丘脑中间神经元已经相当 由于其在总神经元群体中的稀疏性而被忽视。然而，它们广泛的树枝状分支 几乎覆盖了整个细胞核，加上我的初步数据，指出了一个重要的作用， 这些细胞在丘脑功能中的作用。丘脑中间神经元树突能够释放突触小泡， 挑战了神经元输入和输出结构的传统定义，同时大大提高了它们的能力， 复杂的计算令人感兴趣的是，局部丘脑中间神经元也能够形成多种多样的神经元， 不常见的突触关系，包括三元突触。该项目的主要概念目标是 目的是定义支配树突状信号整合的规则，并定义这些规则的功能作用。 中间神经元在典型的丘脑皮层回路中起作用。我假设独特的结构特征 独特的功能。具体地说，我预测，电紧张隔离的树突位置，使许多 编码过程同时发生，并独立于索马。因此，丘脑中间神经元 为研究神经元计算的基本原理提供了独特的机会， 三重抑制在哥伦比亚大学与赞助商教授克里斯梅金森和共同赞助商 教授Liam Paninksi，我将使用最新一代的高增益电压指示器和体外多光子， 在体内成像，以调查上述迫切的问题。这个奖学金代表了一个实质性的 在最先进的成像和计算神经科学技术的高质量培训的机会， 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 通过观察和操纵丘脑局部中间神经元的活动对丘脑功能的影响 振荡我还将应用合成突触输入来探测精确的输入分布模式， 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 将被用来建立现实和良好的约束计算机模拟，以进一步测试精确的机制， 形成感受野结构。我希望能发现，中间神经元作为一个完整的成员， 丘脑皮层回路，并通过他们的研究深入了解神经元计算的基本概念。 审讯展望未来，我希望在这里概述的概念和技术进步的基础上， 揭示感官知觉的致病机制以及丘脑中间神经元在 疾病