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

正在发育的动物大脑中形成的神经元发出电信号，像波一样在大脑的大部分区域传播。脑电波对正常的大脑发育至关重要。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，一种特殊类型的神经元被确定为这些波的起搏器或触发器。这个项目将研究这些神经元是如何触发自发波的。该项目将利用一只老鼠，它可以用光刺激这些神经元。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，使它们能够产生电波。该项目将为本科生和研究生提供机会，在两位在这些领域具有独特专业知识的合作首席研究员的指导下，进行涉及理论和实验生物学的跨学科研究。重点将放在积极征聘妇女充分参与该项目的计算方面。该项目研究了大脑皮层中发育中的氨基丁酸能中间神经元的内在电特性如何使它们在早期发育过程中启动自发的电活动波。先前的遗传和药理学数据表明，这些神经元在早期发育过程中是兴奋的，是小鼠胚胎第18天至出生后第3天大脑皮层自发活动波的主要起搏器。gaba能神经元的详细输入：输出关系将通过在dlx5/6通道-视紫红质小鼠中使用校准的光学刺激并通过细胞外电极阵列记录神经元的输出来确定。将构建基于电导的神经元模型，以反映在种群中遇到的内在特性的多样性。模型神经元将被连接到突触回路中，以确定所测量的特性是否会导致回路中的起搏活动。通过系统地改变模型中的固有特性，将确定对起搏器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来确定神经元的内在特性如何决定大脑中的电路输出。

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.