BRAIN EAGER: Tuning the Intrinsic Computational Properties of Neurons to Changing Circuit Outputs during Early Brain Development

大脑渴望：在早期大脑发育过程中调整神经元的内在计算特性来改变电路输出

• 批准号: 1541133
• 负责人: William Moody
• 金额: $ 30万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1541133&HistoricalAwards=false
• 关键词: BRAIN; EAGER; Tuning; Intrinsic; Computational

Neurons that are being formed in the brain of a developing animal send out electrical signals that spread like waves over large parts of the brain. The waves are essential for normal brain development. The goal of this project is to find out how this spontaneous electrical activity controls brain development. Recently, a specific type of neuron has been identified as being the pacemaker, or trigger, for these waves. This project will study how these neurons trigger the spontaneous waves. The project will take advantage of a mouse that allows these neurons to be stimulated using light. The responses of the neurons to these stimuli will be monitored, and the results will be used to make computer models of the neurons. These models will reveal the properties of these neurons that allow them to produce the waves. The project will offer opportunities for undergraduate and graduate students to be trained in interdisciplinary research that involves both theoretical and experimental biology, under the guidance of two collaborating principal investigators with unique expertise in these areas. Emphasis will be placed on actively recruiting women into full participation in the computational aspects of the project.This project investigates how the intrinsic electrical properties of developing GABAergic interneurons in the cerebral cortex allow them to initiate spontaneous waves of electrical activity during early development. Previous genetic and pharmacological data indicate that these neurons, which are excitatory during early development, are the primary pacemakers for waves of spontaneous activity in the mouse cortex between embryonic day 18 and and postnatal day 3. The detailed input:output relations of GABAergic neurons will be determined by using calibrated optical stimulation in a dlx5/6 channel-rhodopsin mouse and by recording the outputs of the neurons with extracellular electrode arrays. Conductance-based models of the neurons will be constructed that reflect the diversity of intrinsic properties that are encountered in the population. The model neurons will be connected into synaptic circuits to determine whether the measured properties lead to pacemaking activity in the circuit. By systematically varying the intrinsic properties in the model, aspects of the intrinsic properties that are critical for pacemaking function will be determined. If successful, this project will provide a new high-throughput method for determining how the intrinsic properties of neurons determine circuit output in the brain.

正在发育中的动物大脑中形成的神经元会发出像波像波一样在大脑大部分地区的电信号。 波浪对于正常的大脑发育至关重要。 该项目的目的是找出这种自发的电活动如何控制大脑发育。 最近，对于这些波浪，已确定了一种特定类型的神经元为起搏器或触发。该项目将研究这些神经元如何触发自发波。 该项目将利用鼠标，允许使用光刺激这些神经元。 神经元对这些刺激的反应将受到监测，结果将用于使神经元的计算机模型。 这些模型将揭示这些神经元的特性，使它们能够产生波。 该项目将为本科生和研究生提供跨学科研究的培训，涉及理论和实验生物学，并在两位合作的主要研究人员的指导下，在这些领域具有独特的专业知识。 将重点放在积极招募妇女参与该项目的计算方面。该项目研究如何在大脑皮层中开发GABA能中间神经元的内在电性能使她们能够在早期开发过程中发起自发性电波。 以前的遗传学和药理数据表明，这些神经元在早期发育过程中是激发的，是在胚胎第18天和产后第3天之间在小鼠皮层中自发活性波和第3天之间自发活性的主要进步剂。详细输入：使用校准的dlx5/6通道中的gabaerm prounters的输出关系，以确定dlx5/6的输出关系。具有细胞外电极阵列。 将构建基于电导的神经元模型，以反映人群中遇到的内在特性的多样性。 模型神经元将连接到突触电路中，以确定测得的特性是否导致电路中的起搏活动。 通过系统地改变模型中的固有特性，将确定对起搏功能至关重要的内在特性的各个方面。 如果成功，该项目将提供一种新的高通量方法，以确定神经元的内在特性如何确定大脑中的电路输出。