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.

发育中的动物大脑中正在形成的神经元发出电信号，像波一样传播到大脑的大部分区域。这些波对正常的大脑发育是必不可少的。这个项目的目标是找出这种自发的电活动是如何控制大脑发育的。最近，一种特定类型的神经元被发现是这些波的起搏器或触发器。这个项目将研究这些神经元如何触发自发波。该项目将利用一种鼠标，使这些神经元可以用光刺激。这些神经元对这些刺激的反应将被监测，结果将被用来制作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机会，在两名在这些领域具有独特专业知识的合作首席研究人员的指导下，接受涉及理论和实验生物学的跨学科研究方面的培训。该项目的重点是积极招募女性充分参与该项目的计算方面。该项目调查大脑皮质中正在发育的GABA能中间神经元的内在电特性如何使她们能够在发育早期启动自发的电波活动。以往的遗传学和药理学数据表明，这些神经元在发育早期是兴奋性的，是从胚胎第18天到出生后第3天小鼠大脑皮质自发活动波的主要起搏器。详细的输入：输出关系将通过在Dlx5/6通道-视紫红质小鼠上使用校准的光刺激和记录神经元的输出来确定。将构建基于电导的神经元模型，以反映种群中遇到的内在属性的多样性。模型神经元将被连接到突触电路中，以确定测量的特性是否会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，将确定对于起搏功能至关重要的固有特性的各个方面。如果成功，该项目将提供一种新的高通量方法，用于确定神经元的内在属性如何决定大脑中的电路输出。