Circadian output mechanisms in nocturnal and diurnal animals
夜间和白天动物的昼夜节律输出机制
基本信息
- 批准号:10713602
- 负责人:
- 金额:$ 37.55万
- 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:2023-08-01 至 2028-07-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAfricanAnimalsBehaviorBehavioralBiologicalBrainCardiovascular DiseasesChronobiologyCircadian DysregulationCircadian Rhythm Sleep DisordersCommunicationCuriositiesDiseaseEtiologyExhibitsFoodFoundationsGene ExpressionGenesGoalsHealthHumanInvestigationLaboratory miceLife StyleLightLinkMachine LearningMetabolic DiseasesMolecularMood DisordersMusNeuronsNeurophysiology - biologic functionOutcomeOutputPartner in relationshipPeriodicityPhysiological ProcessesPredatory BehaviorResearchRestSignal TransductionSymptomsTimecircadiancircadian biologycircadian pacemakerex vivo imaginggenome editingin vivomolecular clockmultilevel analysisnovelpreferenceprogramsshift worksuprachiasmatic nucleus
项目摘要
Project Summary
Animals have evolved circadian (near-24 h) rhythms to anticipate and adjust their behavior to daily
opportunities and challenges such as mating, food availability, and predation. These behavioral rhythms are
synchronized to the solar day by the central circadian pacemaker, the suprachiasmatic nucleus (SCN). SCN
neurons exhibit daily rhythms in firing rate and clock gene expression that communicate circadian time to the
rest of the brain and body. However, critically, we do not know how SCN signals interact with molecular and
neuronal clocks in downstream neurons to generate circadian outputs. Our lab’s overarching goal is thus to
understand how circadian input from the SCN is encoded by target neurons to ultimately generate diverse
behavioral rhythms that peak at different times of day. To address this, over the next five years, our research
program will focus on several interrelated but independent themes, including defining the “transfer function” for
circadian output circuits, determining how molecular clocks in target neurons contribute to behavioral
rhythmicity, and understanding how target neurons integrate diverse inputs to generate behavioral rhythms.
We propose that endogenous rhythmicity in downstream neurons and daily input from SCN neurons are each
required to drive appropriately timed circadian behavioral outputs. Here, we will use multi-level analysis at the
molecular, circuit, and behavioral levels including targeted genomic editing of clock genes, in vivo and ex vivo
imaging of rhythmic neurons, and machine learning analysis of behavior to dissect circadian output circuitry in
two complementary species, the nocturnal laboratory mouse and the diurnal African striped mouse. Curiously,
molecular and neuronal activity rhythms in the SCN peak at similar times in diurnal and nocturnal animals. How
does an ostensibly identical SCN rhythm determine these dramatically different temporal niches? Our
approach will allow us to address this and other long-standing questions in chronobiology by identifying both
the mechanisms that temporally organize behaviors and the differences in molecular and neural function that
decide an animal’s temporal niche preference. Identifying the genes, neurons, and circuits that regulate the
timing of behavior in both laboratory mice and striped mice will also provide a novel framework for
understanding the biological basis of chronotype in humans and the etiology of circadian rhythm sleep
disorders. The discoveries we will make through our research program can generalize beyond circadian
biology to reveal fundamental mechanisms linking genes and circuits to behavior.
项目摘要
动物已经进化了昼夜节律(接近24 h)的节奏,以预测并调整其行为每天
交配,粮食可用性和掠夺等机会和挑战是
由中央苏联起搏器(SCN)同步到太阳日。
神经元在发射速率和时钟基因表达中表现出每天的节奏
然而,其余的大脑和身体,我们不知道Scnals与分子相互作用
下游神经元中的神经元时钟可产生昼夜节律输出。
了解SCN的昼夜节律输入是如何由目标神经元编码的,以最终产生多样化
在接下来的五年中,在不同时间达到顶峰的行为节奏
程序将重点介绍分层但独立的主题,包括定义“传输函数”
昼夜节律电路,确定目标神经元中的分子钟如何促进行为
节奏和理解靶向神经元如何整合多种输入以产生行为节奏。
我们建议下游神经元中的内源性节奏和SCN神经元的每日输入是
为了驱动定时的昼夜节律行为输出。
分子,电路和行为水平,包括时钟基因的靶向基因组编辑,体内和ex vivo
节奏神经元的成像以及行为的机器学习分析,以剖析昼夜节律电路
两个互补物种,夜间实验室小鼠和昼夜的非洲条纹小鼠。
SCN峰的分子和神经元活性节奏在昼夜夜间动物的相似时间。
表面上相同的SCN节奏是否决定了巨大的暂时壁ni
方法将使我们能够通过识别两者来解决计时生物学中的这个问题和其他长期立式问题
暂时性地组织行为以及分子和神经侵入侵入侵入侵入侵入侵犯侵入侵蚀性的机制的机制
确定动物的暂时性偏好。
实验室小鼠和条纹小鼠的行为时机还将为
了解人类时型的生物学基础和昼夜节律睡眠的病因
疾病。我们将通过我们的研究计划进行的发现
生物学启示将基因和电路与行为联系起来的基本机制。
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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{{ truncateString('JEFFREY R JONES', 18)}}的其他基金
Hypocretinergic integration of circadian rhythms and sleep
昼夜节律和睡眠的低泌尿素整合
- 批准号:
9386665 - 财政年份:2016
- 资助金额:
$ 37.55万 - 项目类别:
Linking Molecular and Electrical Rhythms in the Brain's Biological Clock
连接大脑生物钟中的分子节律和电节律
- 批准号:
8704746 - 财政年份:2012
- 资助金额:
$ 37.55万 - 项目类别:
Linking Molecular and Electrical Rhythms in the Brain's Biological Clock
连接大脑生物钟中的分子节律和电节律
- 批准号:
8546210 - 财政年份:2012
- 资助金额:
$ 37.55万 - 项目类别:
Linking Molecular and Electrical Rhythms in the Brain's Biological Clock
连接大脑生物钟中的分子节律和电节律
- 批准号:
8454841 - 财政年份:2012
- 资助金额:
$ 37.55万 - 项目类别:
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