Structural variation in neuronal circuits as a basis for functional and behavioral individuality

神经元回路的结构变异作为功能和行为个性的基础

基本信息

批准号：
10206473
负责人：
BASSEM A HASSAN
金额：
$ 318.7万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10206473
关键词：
Adult Anatomy Animal Behavior Animal Model Animals Behavior Behavioral Behavioral Assay Biological Assay Biological Models Brain Calcium Cells Cellular Morphology Code Cognitive Communities Complex Computer Models Data Data Set Defect Dimensions Disease Disease model Dorsal Drosophila genus Drosophila melanogaster Electron Microscopy Environmental Risk Factor Evolution Exhibits Female Foundations Funding Genes Genetic Genetic Models Goals Head Human Image Individual Individuality Injury Interneurons Investigation Knowledge Label Light Link Lobe Mammals Maps Microscope Modeling Monitor Monozygotic twins Morphology Nature Nervous System control Nervous system structure Neurons Odors Organism Phenotype Population Proteins Research Research Personnel Resolution Resources Sensory Shapes Signal Transduction Stimulus Stochastic Processes Structure Structure-Activity Relationship Synapses System Technology Testing Translating Variant Visual system structure Weight Work approach behavior comparative connectome connectome data fly in vivo in vivo calcium imaging individual variation information processing insight male neural network neuronal circuitry novel strategies olfactory sensory neurons optogenetics postsynaptic predictive modeling preference presynaptic reconstruction relating to nervous system response sex skills tool trait two-photon voltage

项目摘要

Project Summary A fundamental gap in our knowledge of the nervous system is understanding how variations in wiring and connectivity of neuronal circuits relate to variability in neural computations and behavior. This gap has arisen because anatomical connectivity and function are typically studied separately. Here, we will assemble a team of researchers with complementary skills to tackle this problem. We will combine several technologies developed in our labs, including in vivo calcium imaging during behavior to study neuronal population activity during perceptually-guided behaviors and high-throughput electron microscopy (EM) to extract the connectivity of an underlying network essential for that behavior. To do so, we will use Drosophila melanogaster as a model system because it has a powerful genetic toolkit, tractable number of neurons, is amenable to large-scale behavioral screens, and is a realistic target for comparative whole-brain connectomics. This makes the fly an excellent model to develop a comprehensive approach to characterize neuronal circuits. We will apply our new approach to investigate how population codes, network connectivity, and structure-function relationships differ between individuals. Although it is well known that individuals, as well as males and females, exhibit variable behaviors, little is understood about how variations in neuronal wiring and connectivity relate to variations in neural computation and ultimately behavior. In our first aim, we will compare population codes, wiring, and connectivity between multiple isogenic individuals that exhibit differences in visually-guided approach behavior. In a second aim, we will apply similar approaches to investigate differences in odor preference behavior. We will test how stochastic brain asymmetry, weighting of sensory signals, and repertoire of local interneurons influence computations within individual brains. Analyzing structure-function relationships across individuals will examine the tradeoff between neuronal circuit precision and variability, and reveal how specific variations shape information processing and behavior. We will generate models predicting neuronal function and behavior from circuit wiring and neuronal structure. Our work will be among the first to compare whole-brain, synaptic-resolution connectomes of multiple individuals to reveal fundamental constraints on functional network organization and discover how circuit variability supports individuality.

项目概要我们对神经系统知识的一个根本差距是理解神经线路和神经系统的变化是如何发生的。神经元回路的连接性与神经计算和行为的可变性有关。这个差距已经出现了因为解剖连接性和功能通常是分开研究的。在这里，我们将组建一支团队研究人员具有互补的技能来解决这个问题。我们将结合多项开发的技术在我们的实验室中，包括行为期间的体内钙成像，以研究行为期间的神经元群活动感知引导行为和高通量电子显微镜（EM）来提取该行为所必需的底层网络。为此，我们将使用果蝇作为模型系统因为它拥有强大的遗传工具包、易于处理的神经元数量、适合大规模的行为屏幕，并且是比较全脑连接组学的现实目标。这使得苍蝇成为一个极好的模型来开发表征神经元回路的综合方法。我们将应用我们的新方法来研究人口代码、网络连接和结构功能如何个体之间的关系是不同的。尽管众所周知，个人，以及男性和女性，表现出可变的行为，但人们对神经元布线和连接的变化如何与神经计算和最终行为的变化。在我们的第一个目标中，我们将比较人口代码，多个同基因个体之间的布线和连接在视觉引导方法中表现出差异行为。第二个目标是，我们将应用类似的方法来研究气味偏好的差异行为。我们将测试大脑的随机不对称性、感觉信号的权重以及局部神经元的能力如何。中间神经元影响个体大脑内的计算。分析结构与功能的关系个人将检查神经元回路精度和变异性之间的权衡，并揭示具体如何变化塑造信息处理和行为。我们将生成预测神经元功能的模型电路布线和神经元结构的行为。我们的工作将是第一个比较全脑、多个个体的突触解析连接体揭示功能网络的基本约束组织并发现电路可变性如何支持个性。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Colony size buffers interactions between neonicotinoid exposure and cold stress in bumblebees.

蜂群大小缓冲了大黄蜂新烟碱暴露与冷应激之间的相互作用。

DOI：
发表时间：
2023-07-26
期刊：
影响因子：
0
作者：
Easton;Thuma, Jessie A;Cronin, Kayleigh;Melone, Gigi;Laskowski, Madalyn;Smith, Matthew A Y;Pasadyn, Cassandra L;de Bivort, Benjamin L;Crall, James D
通讯作者：
Crall, James D

Autophagy in synapse formation and brain wiring.

突触形成和大脑接线中的自噬。

DOI：
发表时间：
2023-10
期刊：
影响因子：
13.3
作者：
Hassan, Bassem A;Hiesinger, P Robin
通讯作者：
Hiesinger, P Robin

Numerical discrimination in Drosophila melanogaster.

果蝇的数字歧视。

DOI：
发表时间：
2023-07-25
期刊：
影响因子：
8.8
作者：
Bengochea, Mercedes;Sitt, Jacobo D;Izard, Veronique;Preat, Thomas;Cohen, Laurent;Hassan, Bassem A
通讯作者：
Hassan, Bassem A

Neuromodulation and Individuality.

神经调节和个性。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Maloney; Ryan T
通讯作者：
Ryan T

EGFR-dependent suppression of synaptic autophagy is required for neuronal circuit development.

EGFR 依赖性突触自噬抑制是神经元回路发育所必需的。

DOI：
发表时间：
2023-02-06
期刊：
影响因子：
0
作者：
Dutta, Suchetana B;Linneweber, Gerit Arne;Andriatsilavo, Maheva;Hiesinger, Peter Robin;Hassan, Bassem A
通讯作者：
Hassan, Bassem A