At the right time and place – identifying epigenetic and molecular determinants of a developmental learning window
在正确的时间和地点 – 识别发育学习窗口的表观遗传和分子决定因素
基本信息
- 批准号:10575177
- 负责人:
- 金额:$ 24.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAdolescentAdultAgeAnimal ModelAreaAuditoryBehaviorBehavioralBirdsBrainBrain regionCellsChromatinChromatin StructureDataData SetDevelopmentEpigenetic ProcessExplosionFemaleFoundationsGenomicsGoalsImmunohistochemistryIndividualInvestigationLearningMemoryMethodsMolecularMolecular BiologyMolecular ProfilingNeuronal PlasticityOutcomePatternPhasePhosphorylationPopulationProcessProductivityPropertyProsencephalonPublishingRNAResearchResearch PersonnelRibosomal Protein S6ShapesSongbirdsSystemTechniquesTechnologyTestingTimebrain cellcell typedevelopmental neurobiologyexperiencehatchinginnovationinsightmalemolecular markermultiple omicsneural networknovelprogramsrecruitremediationresponsesexsingle cell sequencingspatial integrationtraittranscriptome sequencingtranscriptomicszebra finch
项目摘要
Summary.
Despite the plethora of ways that developmental experience influences long-term patterns of behavior, our
mechanistic understanding of how this occurs is limited. The long-term goal of this research program is to
elucidate the intersection of maturational and experience-dependent mechanisms that support behavioral
acquisition across development. The objective of this application is to identify the epigenetic and molecular
signatures of select cells recruited for developmental learning in juveniles. Here, we build on our recent
preliminary data that repeatable, spatially-discreet cell populations initiate a molecular response required for
memory formation at an age when learning is possible, but not before, and differently between males and
females. This provides a unique opportunity to track the changes that occur within a brain region as
development proceeds and comes “on-line” for encoding experience such that it determines adult behavioral
patterns. In contrast to the explosion of sequencing technology-based discoveries about brain cells in adults,
only a few factors are known to track with developmental learning. Identifying the properties of individual cells
and their networks as they shift functionally across juvenile development would be useful for discovery of other
brain systems that undergo developmental functional fluctuations and ultimately to move towards remediation
efforts and enrichment programs targeted for peak phases of developmental receptivity to experience. The
central hypothesis is that epigenetic and molecular regulatory processes define individual cells and their
relationships differently depending on an individual’s age and sex, creating combinations that support learning
at the onset of a natural learning phase. The PI has expertise in mechanisms of brain development and
behavior including epigenetics and molecular biology as means to find causal relationships of juvenile
experience to adult behavior. The co-Investigator’s expertise in single cell sequencing methods and analysis is
complementary. The objectives will be accomplished by pursing two specific aims 1) To identify properties of
the auditory forebrain that support molecular activation required for behavioral effects, and 2) To predict cell
responsivity based on baseline chromatin accessibility and RNA profiles. A combination of state-of-the-art
sequencing methods, and innovative analysis across platforms and datasets, will discover new relationships
between chromatin structure and RNA populations, new cell subtypes, and the relationships between them,
that predict the ability to learn in sex-specific ways. Using a molecular marker for cells recruited for learning,
we will then co-localize these baseline cell features with functional ones. The proposed research thus begins to
fill a void in developmental neurobiology by applying an unprecedented level of detail to the structural
organization of functional networks. Elucidating and establishing mechanisms underlying the organization of
developing brain to encode experience is the key to breaking through to a new productive era for testing novel
ways that maturation and experience-dependent processes shape neural networks to promote or limit learning.
概括。
尽管发展经历以多种方式影响长期行为模式,但我们的
对这种情况如何发生的机制的理解是有限的。该研究计划的长期目标是
阐明支持行为的成熟机制和经验依赖机制的交叉点
该应用程序的目的是识别表观遗传和分子。
在这里,我们以最近的研究为基础,收集了为青少年的发育学习而招募的精选细胞的特征。
初步数据表明,可重复的、空间离散的细胞群启动了所需的分子反应
记忆的形成是在可以学习的年龄,但在此之前则不然,而且男女之间的情况不同
这提供了一个独特的机会来追踪大脑区域内发生的变化。
发展继续进行,并“在线”编码经验,从而决定成人的行为
与基于测序技术的成人脑细胞发现的爆炸式增长相比,
目前已知只有少数因素可以追踪发育学习。
当它们在青少年发育过程中功能转变时,它们的网络将有助于发现其他
经历发育功能波动并最终走向修复的大脑系统
以及针对体验发展接受能力的高峰阶段的丰富计划。
中心假设是表观遗传和分子调控过程定义了个体细胞及其
根据个人的年龄和性别,建立不同的关系,创造支持学习的组合
在自然学习阶段开始时,PI 拥有大脑发育机制方面的专业知识和知识。
包括表观遗传学和分子生物学在内的行为作为寻找青少年因果关系的手段
共同研究者在单细胞测序方法和分析方面的专业知识是
互补的目标将通过追求两个具体目标来实现: 1) 确定属性
支持行为效应所需的分子激活的听觉前脑,以及 2) 预测细胞
基于基线染色质可及性和 RNA 图谱的响应性。
测序方法以及跨平台和数据集的创新分析将发现新的关系
染色质结构和 RNA 群体、新细胞亚型以及它们之间的关系,
使用分子标记来预测为学习而招募的细胞的学习能力,
然后,我们将把这些基线细胞特征与功能特征共同定位,从而开始拟议的研究。
通过将前所未有的细节水平应用于结构神经生物学,填补了发育神经生物学的空白
阐明和建立组织的机制。
开发大脑来编码经验是突破小说测试新生产力时代的关键
成熟和依赖经验的过程塑造神经网络以促进或限制学习的方式。
项目成果
期刊论文数量(0)
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SARAH E LONDON其他文献
SARAH E LONDON的其他文献
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{{ truncateString('SARAH E LONDON', 18)}}的其他基金
Linking Juvenile Experiences with Adult Patterns of Behavior
将青少年经历与成人行为模式联系起来
- 批准号:
10501980 - 财政年份:2022
- 资助金额:
$ 24.6万 - 项目类别:
Linking Juvenile Experiences with Adult Patterns of Behavior
将青少年经历与成人行为模式联系起来
- 批准号:
10620295 - 财政年份:2022
- 资助金额:
$ 24.6万 - 项目类别:
The molecular basis for developmental sensory learning
发展感觉学习的分子基础
- 批准号:
7595800 - 财政年份:2008
- 资助金额:
$ 24.6万 - 项目类别:
The molecular basis for developmental sensory learning
发展感觉学习的分子基础
- 批准号:
7404882 - 财政年份:2008
- 资助金额:
$ 24.6万 - 项目类别:
Developmental Differences in Brain Androgen Synthesis
大脑雄激素合成的发育差异
- 批准号:
6671466 - 财政年份:2002
- 资助金额:
$ 24.6万 - 项目类别:
Developmental Differences in Brain Androgen Synthesis
大脑雄激素合成的发育差异
- 批准号:
6735610 - 财政年份:2002
- 资助金额:
$ 24.6万 - 项目类别:
Developmental Differences in Brain Androgen Synthesis
大脑雄激素合成的发育差异
- 批准号:
6446584 - 财政年份:2002
- 资助金额:
$ 24.6万 - 项目类别:
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