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: 10467357
• 负责人: Jane Yi
• 金额: $ 7.19万
• 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/10467357
• 关键词: 3-Dimensional; Address; Amplifiers; Arithmetic; Arousal; Attention; BRAIN initiative; Behavior; Behavioral; Biophysical Process; Brain; Brain region; Calcium; Cannulas; Cell Nucleus; Cell physiology; Cells; Cellular Structures; Code; Communication; Complement; Complex; Computer Models; Computer Simulation; Data; Data Set; Dendrites; Detection; Development; Disease; Distal; Electroencephalography; Electrophysiology (science); Evaluation; Fellowship; Generations; Glutamates; Goals; Home; Image; In Vitro; Individual; Interneuron function; 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; Touch sensation; Training; Trees; Triad Acrylic Resin; 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; multi-electrode arrays; multi-photon; multiphoton imaging; neural circuit; neuronal cell body; next generation; novel; operation; optogenetics; receptive field; reconstruction; relating to nervous system; 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 老鼠体感丘脑参与包括感觉处理，睡眠在内的基本过程 和病理性的节奏行为，例如癫痫发作。当地的丘脑中间神经元已经相当多 由于它们在神经元人群中的稀疏而被忽视。但是，它们广泛的树突状养育 几乎涵盖了细胞核的整个广度，以及我的初步数据，表明了一个重要的作用 对于丘脑功能中的这些细胞。丘脑间神经元树突能够释放突触囊泡， 无视神经元输入和输出结构的传统定义，同时大大提高了其能力 复杂的计算。感兴趣的是，局部丘脑中间神经元也能够形成多种多样的 不常见的突触关系，包括三合会突触。该项目试图的主要概念目标 地址是定义控制树突信号集成的规则，并定义功能作用 中间神经元在规范的丘脑皮层电路中发挥作用。我假设独特的结构特征启用了 独特的功能。具体而言，我预测电孤立的树突状位置可以使许多 编码过程同时且独立于SOMA进行。因此，丘脑中间神经元 为研究神经元计算的基本原理带来独特的机会，包括歧义角色 三合会抑制作用。与赞助商克里斯·麦金森（Chris Makinson）和共同赞助者一起在哥伦比亚大学举行 Liam Paninksi教授，我将在体外使用最新一代的高增益电压指标和多光子 在体内成像，以研究上面概述的命令性问题。该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中进行高质量培训的机会 方法可以补充我在神经生物学和电生理学方面的背景。我的目标是解决 局部间神经元在丘脑功能中的影响通过观察和操纵丘脑的活性 振荡。我还将以精确输入分布模式和 丘脑中间神经元中树突状相结合的生物物理机制。这些实验的数据 将用于构建现实且良好的计算机模拟，以进一步测试精确的机制 塑造接受场结构。我希望发现中间神经元充当不可或缺的成员 丘脑皮层电路，并通过其洞察神经元计算的基本概念 审讯。向前迈进，我希望在这里概述的概念和技术进步基础上 发现感知感知涉及的致病机制和丘脑中间神经元在 疾病。