Dissecting the functional organization of the serotonergic system in C. elegans
剖析线虫血清素系统的功能组织
基本信息
- 批准号:10542483
- 负责人:
- 金额:$ 5.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-19 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:Animal FeedAnimalsArchitectureBehaviorBiological ModelsBrainCaenorhabditis elegansCalciumCellsComplexCuesDataDesire for foodEnzymesEquilibriumFoodGenesGeneticHumanImageIngestionLocomotionMammalsMapsMediatingMembrane Transport ProteinsMonitorNervous system structureNeuronsNeurosciencesOrthologous GenePatternPharmaceutical PreparationsPublishingSerotonergic SystemSerotoninSignal TransductionSiteSynapsesSystemWorkbehavioral responsecell typeconnectomeimaging approachin vivomind controlneural circuitreceptorrelating to nervous systemresponseserotonin receptortool
项目摘要
The serotonergic system impacts a wide range of human behaviors and is a common target of psychiatric
drugs. In mammals, neural circuits that receive serotonergic inputs are composed of diverse cell types, each of
which expresses a subset of 14 distinct serotonin (5-HT) receptors. The impact of 5-HT release on circuit function
involves the coordinated activation of many receptor types in distinct neurons. However, we do not yet
understand the fundamental principles by which 5-HT acts at many sites within a circuit to coherently alter circuit
function. Here, we propose to resolve this question in C. elegans. The C. elegans nervous system is particularly
attractive for whole-circuit questions in neuroscience because it consists of exactly 302 neurons, every neuron
can be identified in every animal, the synaptic connections between these neurons (the “connectome”) have
been fully defined, and excellent genetic tools can be used to manipulate single cells in this well-defined system.
Moreover, this animal’s transparency allows us to use cutting-edge imaging approaches – including whole-brain
calcium imaging – to monitor neural activity in freely-behaving animals. Importantly, 5-HT signaling is well-
conserved from C. elegans to mammals: C. elegans orthologs of human genes encode for 5-HT synthesis
enzymes (TPH), vesicular and membrane transporters (VMAT, SERT), 5-HT receptors (5-HT1, 5-HT2, etc) and
more. Thus, studies of this animal should reveal general principles of 5-HT function that can be subsequently
applied to more complex animals. The studies in this proposal build off recently published work from my lab and
new preliminary data. In a recent study, we found that food ingestion by C. elegans activates a specific 5-HTergic
neuron, called NSM, whose release of 5-HT drives slow locomotion while animals feed. We also showed that
this neuron’s dynamical response to food ingestion controls locomotion dynamics: different patterns of 5-HT
release drive different locomotion changes. In new preliminary data, we have systematically examined how
patterned 5-HT release impacts locomotion, begun mapping out the 5-HT receptors that mediate these effects,
and developed an approach to monitor 5-HT-induced changes in whole-brain activity. In the current proposal,
we will use this well-constrained experimental paradigm and these cutting-edge imaging approaches to probe
the functional architecture of the 5-HT system and examine how 5-HT receptors interact to control brain function.
Specifically, we will first map out the 5-HT receptors and circuits that mediate behavioral responses to different
patterns of 5-HT release (Aim 1). In a second aim, we will use new calcium imaging approaches to determine
how different patterns of 5-HT release engage different 5-HT receptor types to alter whole-brain activity (Aim 2).
Finally, we will also examine how aversive cues that antagonize 5-HT signaling modulate the function of
serotonergic circuits, allowing animals to balance aversive and appetitive inputs (Aim 3). These studies will reveal
how patterned 5-HT release engages specific 5-HT receptor types to impact brain function, yielding a new
framework for 5-HT circuit organization and function.
血清素能系统广泛影响人类行为,是精神病学的共同目标
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Steven Willem Flavell其他文献
Steven Willem Flavell的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Steven Willem Flavell', 18)}}的其他基金
Neural Mechanisms that Underlie Flexible Sensory Control of Behavioral States in C. elegans
线虫行为状态灵活感觉控制的神经机制
- 批准号:
10659880 - 财政年份:2023
- 资助金额:
$ 5.83万 - 项目类别:
Brain-wide representations of behavior during aversive internal states in C. elegans
线虫厌恶的内部状态下的全脑行为表征
- 批准号:
10638999 - 财政年份:2023
- 资助金额:
$ 5.83万 - 项目类别:
Dissecting the functional organization of the serotonergic system in C. elegans
剖析线虫血清素系统的功能组织
- 批准号:
10334517 - 财政年份:2020
- 资助金额:
$ 5.83万 - 项目类别:
Dissecting the functional organization of the serotonergic system in C. elegans
剖析线虫血清素系统的功能组织
- 批准号:
10725038 - 财政年份:2020
- 资助金额:
$ 5.83万 - 项目类别:
Dissecting the functional organization of the serotonergic system in C. elegans
剖析线虫血清素系统的功能组织
- 批准号:
10554333 - 财政年份:2020
- 资助金额:
$ 5.83万 - 项目类别:
Neuromodulatory control of collective circuit dynamics in C. elegans
线虫集体回路动力学的神经调节控制
- 批准号:
10207798 - 财政年份:2017
- 资助金额:
$ 5.83万 - 项目类别:
相似海外基金
The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
- 批准号:
EP/Z000920/1 - 财政年份:2025
- 资助金额:
$ 5.83万 - 项目类别:
Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
- 批准号:
FT230100276 - 财政年份:2024
- 资助金额:
$ 5.83万 - 项目类别:
ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
- 批准号:
MR/X024261/1 - 财政年份:2024
- 资助金额:
$ 5.83万 - 项目类别:
Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
- 批准号:
DE240100388 - 财政年份:2024
- 资助金额:
$ 5.83万 - 项目类别:
Discovery Early Career Researcher Award
Zootropolis: Multi-species archaeological, ecological and historical approaches to animals in Medieval urban Scotland
Zootropolis:苏格兰中世纪城市动物的多物种考古、生态和历史方法
- 批准号:
2889694 - 财政年份:2023
- 资助金额:
$ 5.83万 - 项目类别:
Studentship
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
- 批准号:
2842926 - 财政年份:2023
- 资助金额:
$ 5.83万 - 项目类别:
Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
- 批准号:
NC/X001644/1 - 财政年份:2023
- 资助金额:
$ 5.83万 - 项目类别:
Training Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
- 批准号:
2337595 - 财政年份:2023
- 资助金额:
$ 5.83万 - 项目类别:
Continuing Grant
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
- 批准号:
2232190 - 财政年份:2023
- 资助金额:
$ 5.83万 - 项目类别:
Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
- 批准号:
23K17514 - 财政年份:2023
- 资助金额:
$ 5.83万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)