Molecular and neuronal mechanisms of complex behaviors
Molecular and neuronal mechanisms of complex behaviors
批准号:
8697947
负责人:
Mark Alkema
金额:
$35.05万
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-05-01 至 2018-04-30
关键词:
AccountingAddressAffectAnimalsBehaviorBehavior DisordersBehavioralBrainBrain DiseasesCaenorhabditis elegansCalcium ChannelClinicalCodeComplexCoupledDecision MakingDetectionDiseaseEtiologyFamilial Hemiplegic MigraineFeedbackFunctional disorderGenesGeneticGenetic ScreeningGoalsHead MovementsHereditary DiseaseHumanHyperactive behaviorImageInvertebratesIon ChannelLifeLinkLocomotionMediatingMethodsMigraineModelingMolecularMolecular TargetMonitorMotorMovementNervous system structureNeurologicNeuromodulatorNeuronsNeurotransmittersOpticsOrganismOutputPerformancePhasePhenotypePhysiologicalPreparationProcessResearchResolutionSchizophreniaSensorySensory ProcessSignal TransductionStimulusSynapsesSystemTestingTimeTranscendUncertaintybehavior changegain of functiongain of function mutationgenetic analysisin vivolearned behaviormental statemonoaminemutantnervous system disorderneural circuitneural modelneuromechanismnoveloptogeneticspleiotropismpresynapticprogramspublic health relevancereceptorrelating to nervous systemresearch studyresponsetooltreatment strategyvoltage
中文摘要
项目摘要
这项研究的目的是了解神经系统是如何协调复杂的
行为复杂的行为需要独立神经回路的时间协调。尽管
广泛的认识是,神经递质和离子通道的作用可以微调神经递质的输出,
神经回路,有一个令人惊讶的有限的了解如何神经系统指挥
连续的激活和抑制神经元的组装以协调行为。的改变
神经递质系统和离子通道长期以来与多种神经系统疾病的病因学有关。
神经系统疾病,强调需要制定有效的方法,可以直接关系到
特定神经元回路的协调活动以实现复杂行为。为了阐明
神经系统在分子和神经水平上协调复杂的行为,我们正在研究
C.这是一个高度协调的运动序列,需要感觉
处理,决策和独立运动程序的时间协调。我们
一项分析揭示了突触前电压门控钙通道(CaV2)和单胺
通过快速作用的突触激活在时间上协调反应的不同阶段
离子型受体和慢作用代谢型受体的突触外激活。我们将使用
Ca2+成像和光遗传学用于确定神经元活动之间的时间和因果关系
和逃避反应的子运动程序。为了确定独立的运动程序
在复合运动序列的执行中是联系在一起的,我们将研究逆转是如何与
逃避反应时的转向行为我们将使用突变分析来检验
检测或抑制后反弹机制解释了这些子运动的顺序激活
程序.由于神经调质通过抑制突触活性来精确调节突触活性,
突触前电压门控Ca2+通道(CaV2),我们将定义新的CaV2信号传导组件,
在电路功能中调节CaV2通道。我们的秀丽隐杆线虫CaV2功能获得性突变体提供了
家族性偏瘫性偏头痛的第一个无脊椎动物模型,并提供了新的工具来修改电路
逃避反应的表现。对C.
elegans将阐明类似的机制,协调复杂的行为,在更复杂的
包括人类在内的动物。我们期望我们的研究将对我们的理解产生重大影响
神经调质和电压门控钙通道如何影响行为中的电路功能,
神经系统疾病,并将提供新的分子靶点和治疗这些战略
疾病
英文摘要
Project Summary
The goal of the proposed research is to understand how the nervous system orchestrates complex
behavior. Complex behaviors require the temporal coordination of independent neural circuits. Despite
widespread recognition that the action of neurotransmitters and ion channels fine tune the output of
neural circuits, there is a surprisingly limited understanding of how the nervous system directs
sequential activation and inhibition of assemblies of neurons to orchestrate behavior. Alterations in the
neurotransmitter systems and ion channels have long been implicated in the etiology of a variety of
neurological disorders, underlining the need to develop effective approaches that can directly relate
the coordinated activity of specific neuronal circuits to complex behaviors. To elucidate how the
nervous system orchestrates complex behaviors at the molecular and neural level we are studying the
C. elegans escape response, which is a highly orchestrated motor sequence that requires sensory
processing, decision-making and the temporal coordination of independent motor programs. Our
analysis has unraveled how presynaptic voltage-gated Ca2+ channels (CaV2) and monoamines
temporally coordinate different phases of the response through synaptic activation of fast-acting
ionotropic receptors, and extra-synaptic activation of slow-acting metabotropic receptors. We will use
Ca2+ imaging and optogenetics to define temporal and causal relationship between neuronal activity
and the sub-motor programs of the escape response. To determine how independent motor programs
are linked in the execution of a compound motor sequence we will study how reversals are coupled to
turning behavior during the escape response. We will use mutant analysis to test if coincidence
detection or post-inhibitory rebound mechanisms account for sequential activation of these sub-motor
programs. Since neuromodulators precisely regulate synaptic activity through the inhibition of
presynaptic voltage-gated Ca2+ channels (CaV2), we will define novel CaV2 signaling components that
regulate CaV2 channels in circuit function. Our C.elegans CaV2 gain-of-function mutant provides the
first invertebrate model for familial hemiplegic migraine and provides novel tool to modify circuit
performance in the escape response. The mechanisms that organize activity in the escape circuit of C.
elegans will illuminate similar mechanisms that orchestrate complex behaviors in more complex
animals including humans. We expect that our studies will have a major impact on our understanding
of how neuromodulators and voltage-gated-calcium channels affect circuit function in behavior and
neurological disorders, and will provide new molecular targets and strategies for the treatment of these
diseases.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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批准号:10672430
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项目类别:
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资助金额:$38.19万
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财政年份:2021
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依托单位:
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批准号:10378485
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项目类别:
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资助金额:$36.64万
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依托单位:
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批准号:9133477
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项目类别:
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依托单位:
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依托单位:
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负责人:Mark Alkema
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依托单位:
Analysis of tyraminergic signaling in Caenorhabditis elegans
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批准号:8214652
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项目类别:
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资助金额:$32.25万
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财政年份:2008
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负责人:Mark Alkema
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依托单位:
Analysis of tyraminergic signaling in Caenorhabditis elegans
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批准号:7616486
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项目类别:
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资助金额:$32.77万
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负责人:Mark Alkema
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依托单位:
Molecular and neuronal mechanisms of complex behaviors
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依托单位:
海外基金