Connecting the mechanobiology of tissue and cells in cerebral cortical folding
连接大脑皮质折叠中组织和细胞的力学生物学
基本信息
- 批准号:10402819
- 负责人:
- 金额:$ 50.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-07-15 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAddressAffectAgeAnimal ModelAnimalsAreaAtomic Force MicroscopyAttention deficit hyperactivity disorderAxonBehaviorBilateralBiologicalBiological ModelsBiomechanicsBrainCell NucleusCell physiologyCellsCellular biologyCerebral cortexCerebrumClinical ManagementComputer ModelsComputer SimulationCongenital DisordersDataDendritesDevelopmentDevelopmental ProcessDiffusion Magnetic Resonance ImagingDiseaseEnvironmental Risk FactorEtiologyEventExhibitsFerretsFetal Alcohol Spectrum DisorderFresh TissueGene ExpressionGlial Cell ProliferationGrowthHistologicHumanIndividualKnowledgeLawsLifeLinkMagnetic Resonance ImagingMathematicsMeasurementMeasuresMechanical StressMechanicsMicrogyriaModelingMorphologyNeurobiologyNeurodevelopmental DisorderNeurogliaNeurologicNeuropilNuclearPatternPhosphorus 32PhysicsPhysiologicalPregnancyPremature BirthProcessProductionPropertyRadialSamplingSchizophreniaSeriesShapesSourceStressStructureSurfaceSurgical incisionsSynapsesSystemTemporal SulcusTheoretical modelThickTimeTissue ModelTissuesTranslatingVisionVisual CortexWilliams Syndromeanimal imagingarea striataautism spectrum disorderbiophysical modelbrain cellcell growthcell typecellular developmentcohortexperimental studygray matterimprovedin vivolissencephalymechanical propertiesmigrationmulti-scale modelingnerve stem cellneurogenesisneuronal cell bodypostnatalpostnatal developmentresponsestress statesubventricular zonetissue stresstissue-level behaviorwhite matter
项目摘要
ABSTRACT
The folding patterns observed in the cerebral cortex of individuals affected by many neurodevelopmental
disorders differ from those in typically-developing "control" individuals. The human cerebral cortex folds over
the period from the middle of gestation through the first months of postnatal life. Although much is known about
how the brain develops over this time period, including proliferative activity, morphological maturation of many
cell types, establishment of synaptic connections, development of cortical circuitry, macroscopic growth, and
system-level physiological changes in the brain, relatively little is understood about how these changes relate
to the production of a normal, or abnormal, folding pattern at maturity. Shortcomings in our understanding of
the relationship between cellular-level developmental events and macroscopic behavior (growth and
biomechanical properties of tissue) limit our ability to explain a given folding abnormality in terms of its
neurodevelopmental source, or in terms of potential etiological factors important for a specific
neurodevelopmental disorder. This application proposes a series of studies to link high-precision experimental
measures of brain growth and mechanical properties with computational simulations to advance our
understanding of the biomechanical factors that influence cerebral cortical folding. This combined experimental
and theoretical approach will be used to analyze folding of the ferret cerebral cortex. As with the human brain,
the ferret brain possesses gyri and sulci at maturity, but in contrast to humans, these folds arise postnatally in
ferrets. Specific focus will be placed on the occipital temporal sulcus (OTS), within the primary visual cortex,
which folds relatively late compared to other sulci, concluding by P35. Recently, we have discovered that OTS
formation is severely affected (or that the OTS does not form at all) in ferrets that have undergone bilateral
enucleation at P7. Growth and mechanical properties will therefore be characterized in sighted control (SC)
and bilaterally enucleated on P7 (BEP7) ferrets at 6 time points ranging from P8 through P38. This data will be
integrated with the development of a multiscale theoretical and computational model of brain growth. In Aim 1,
growth will be characterized on a macroscopic scale by in vivo MRI, and on a cellular level by measuring how
P7 enucleation affects proliferation dynamics and changes cell body and neuropil volumes over the period of
cortical folding. In Aim 2, mechanical properties of the tissue will be quantified over the same age range. Shear
moduli of cortical gray matter and developing white matter will be determined using atomic force microscopy.
Tissue stress will be measured by observing tissue deformations following incisions. Tissue stress on a smaller
spatial scale will be inferred from the shapes of nuclei and from the orientation distributions of cellular
processes. In Aim 3, the experimental data from Aims 1 and 2 will be integrated into a model of tissue growth
and deformation, and the validity of the model will be evaluated by observing its ability to recapitulate
differences in folding patterns between SC and BEP7 ferrets.
抽象的
在受许多神经发育影响的个体的大脑皮层中观察到的折叠模式
疾病与典型发育的“对照”个体的疾病不同。人类大脑皮层折叠起来
从妊娠中期到产后头几个月的时期。尽管人们知道很多
大脑在这段时间内如何发育,包括增殖活动、许多细胞的形态成熟
细胞类型、突触连接的建立、皮质电路的发育、宏观生长和
大脑系统级的生理变化,但人们对这些变化之间的关系知之甚少
成熟时产生正常或异常的折叠图案。我们认识上的缺陷
细胞水平发育事件与宏观行为(生长和发育)之间的关系
组织的生物力学特性)限制了我们解释给定折叠异常的能力
神经发育来源,或对于特定的重要潜在病因而言
神经发育障碍。该应用提出了一系列研究来链接高精度实验
通过计算模拟来测量大脑生长和机械特性,以推进我们的研究
了解影响大脑皮层折叠的生物力学因素。本次联合实验
理论方法将用于分析雪貂大脑皮层的折叠。与人脑一样,
雪貂的大脑在成熟时拥有脑回和脑沟,但与人类不同的是,这些褶皱是在出生后出现的
雪貂。具体重点将放在初级视觉皮层内的枕颞沟 (OTS),
与其他脑沟相比,其折叠相对较晚,直到 P35 结束。最近,我们发现OTS
在经历过双边性手术的雪貂中,OTS 的形成受到严重影响(或者根本不形成 OTS)。
P7 去核。因此,生长和机械性能将通过视力控制(SC)来表征
并在 P8 至 P38 的 6 个时间点对 P7 (BEP7) 雪貂进行双侧去核。该数据将是
与大脑生长的多尺度理论和计算模型的发展相结合。在目标 1 中,
将通过体内 MRI 在宏观尺度上表征生长,并通过测量如何在细胞水平上表征生长
P7 摘除会影响增殖动力学并改变细胞体和神经纤维体积。
皮质折叠。在目标 2 中,将在同一年龄范围内量化组织的机械特性。剪切
皮质灰质和发育白质的模量将使用原子力显微镜测定。
将通过观察切口后的组织变形来测量组织应力。组织应力较小
空间尺度将从原子核的形状和细胞的方向分布推断出来
流程。在目标 3 中,目标 1 和 2 的实验数据将整合到组织生长模型中
和变形,并且模型的有效性将通过观察其重演的能力来评估
SC 和 BEP7 雪貂之间折叠模式的差异。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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PHILIP V BAYLY其他文献
PHILIP V BAYLY的其他文献
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{{ truncateString('PHILIP V BAYLY', 18)}}的其他基金
High-Resolution, Anisotropic MR Elastography of the Brain
高分辨率、各向异性脑部 MR 弹性成像
- 批准号:
10317077 - 财政年份:2019
- 资助金额:
$ 50.1万 - 项目类别:
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10471274 - 财政年份:2019
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$ 50.1万 - 项目类别:
Connecting the mechanobiology of tissue and cells in cerebral cortical folding
连接大脑皮质折叠中组织和细胞的力学生物学
- 批准号:
10159333 - 财政年份:2019
- 资助金额:
$ 50.1万 - 项目类别:
Connecting the mechanobiology of tissue and cells in cerebral cortical folding
连接大脑皮质折叠中组织和细胞的力学生物学
- 批准号:
10619447 - 财政年份:2019
- 资助金额:
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10680435 - 财政年份:2019
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$ 50.1万 - 项目类别:
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- 批准号:
10680435 - 财政年份:2019
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10474698 - 财政年份:2019
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