Longitudinal in vivo imaging of synaptic pathologies of Alzheimer's disease
Longitudinal in vivo imaging of synaptic pathologies of Alzheimer's disease
批准号:
9895142
负责人:
Austin Robert Graves
金额:
$45.03万
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
项目状态:
已结题
起止时间:
2020-02-01 至 2022-01-31
关键词:
Adaptive BehaviorsAddressAffectAgeAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease pathologyAlzheimer&aposs disease related dementiaAmyloidAmyloid beta-ProteinAmyloid depositionAnimalsAreaBehavioralBiologicalBiological MarkersBrainBrain regionCellsCessation of lifeChronicCognitiveCognitive deficitsCommunicationDataDementiaDevelopmentDiseaseDisease MarkerDisease ProgressionDisease modelDyesExcitatory SynapseFluorescent DyesFrightFunctional disorderGeneticGlutamate ReceptorHippocampus (Brain)HumanImageImpaired cognitionImpairmentImplantKnock-inKnock-in MouseLabelLeadLearningLigandsMemoryMemory LossMemory impairmentMicroscopyModelingMolecularMolecular ProfilingMonitorMusNeocortexNervous system structureNeurofibrillary TanglesNeuronsNeurosciencesOperative Surgical ProceduresOpticsPHluorinPathogenesisPathologicPathologyPhysiologyPopulationProteinsRodent ModelSignal TransductionSymptomsSynapsesTechniquesTherapeutic InterventionTimeVisualizationaustinbehavior testbehavioral impairmentbehavioral phenotypingbrain cellcognitive functionconditioned fearcraniumeffective therapyexperiencehuman diseasein vivoin vivo imaginginnovationinsightmedical schoolsmemory encodingmemory recallmolecular pathologymouse modelneurological pathologynovelnovel strategiesoverexpressionreal time monitoringrelating to nervous systemserial imagingsynaptic functiontau Proteinstau aggregationtooltwo photon microscopy
中文摘要
突触是神经系统的基本单位,使脑细胞和神经细胞之间的交流成为可能
英文摘要
The synapse is the fundamental unit of the nervous system, enabling communication between brain cells and
providing a substrate for experience-dependent plasticity to drive adaptive behaviors. Altering the strength of
synapses between specific cells or neuronal ensembles is thought to underlie higher brain functions such as
learning and memory, whereas synaptic degradation is observed in many neurological pathologies, such as
Alzheimer's disease (AD) and related dementias. Despite the clear significance of synaptic communication, the
relationship between impaired synaptic function, progression of AD symptoms, and cognitive decline remains
unclear. However, recent breakthroughs in molecular microscopy enable direct imaging of the progression of
pathological synaptic deficits in mouse models of Alzheimer's disease. Our approach is to fluorescently tag
synaptic proteins and AD markers to track them throughout disease progression using in vivo two-photon
microscopy. By imaging large populations of synapses comprising entire cortical and hippocampal circuits, we
strive to gain a detailed understanding of how molecular pathologies affect synaptic physiology and ultimately
give rise to cognitive decline. This approach will yield a detailed time course of the progression of synaptic and
cognitive Alzheimer's pathologies that may reveal effective treatment windows and novel avenues for therapeutic
interventions for human disease.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1038/s41592-023-01871-6
发表时间:
2023-06
期刊:
NATURE METHODS
影响因子:
48
作者:
[Xu, Yu Kang T., Graves, Austin R., Coste, Gabrielle I., Huganir, Richard L., Bergles, Dwight E., Charles, Adam S., Sulam, Jeremias]
通讯作者:
Sulam, Jeremias
Role of metabotropic receptors in regulating intrinsic plasticity in hippocampus
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批准号:7914034
-
项目类别:
-
资助金额:$3.36万
-
财政年份:2010
-
负责人:Austin Robert Graves
-
依托单位:
Role of metabotropic receptors in regulating intrinsic plasticity in hippocampus
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批准号:8047991
-
项目类别:
-
资助金额:$3.08万
-
财政年份:2010
-
负责人:Austin Robert Graves
-
依托单位:
海外基金