Discovery and analysis of brain circuits and cell types affected in autism and schizophrenia
发现和分析受自闭症和精神分裂症影响的大脑回路和细胞类型
基本信息
- 批准号:10100970
- 负责人:
- 金额:$ 80.32万
- 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:2020-09-15 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAmazeAmericanAnatomyBehavioralBiologicalBiological ModelsBrainBrain imagingBrain regionCognitiveCollaborationsCollectionComputer AnalysisComputing MethodologiesDataDevelopmentDiseaseDistantDreamsEconomicsEtiologyFiberFoundationsGeneticGenomeGenotypeGoalsGrantHumanImageInstitutionKnowledgeLarge-Scale SequencingMediatingMental disordersModelingMouse StrainsMusMutationNeuronsNeurosciencesPatientsPhenotypePhotometryPublicationsRecording of previous eventsResearchResolutionSchizophreniaSensorySex DifferencesSiteSocietiesSourceStructureSystemSystems BiologyTestingTimeUniversitiesValidationVariantautism spectrum disorderbasebrain cellcell typecohortconnectome datagenetic analysisgenetic varianthuman datainsightmouse modelneuropsychiatric disorderpreventpsychogeneticssingle-cell RNA sequencingskillssocialultra high resolution
项目摘要
PROJECT SUMMARY
There is now unequivocal evidence that the behavioral and cognitive phenotypes associated with
psychiatric disorders are mediated by perturbations to specific brain circuits, i.e. sets of strongly
anatomically and functionally connected brain structures. However, there are currently no
unbiased computational approaches to implicate disease-related circuits, in a brain-wide fashion
and at a high spatial resolution, and then to connect abnormalities in these circuits to specific
patient phenotypes. The main goal of the proposal is to develop and optimize a computational
approach which will make it possible, for the first time and at an unprecedented resolution, to
discover functional brain circuits involved in mental disorders. The proposed approach is based
on synergistic analyses of genetics data, ultra-high-resolution expression and brain-wide
connectome data – available for the same mouse strain, and in a common coordinate system. An
important virtue of the approach is that it is based exclusively on genome- and brain-wide data
and therefore is not biased towards any prior hypothesis about disorders' etiology. We specifically
propose Aim 1. Identify brain circuits and associated cell types primarily affected by genetic
insults in autism spectrum disorder (ASD) and schizophrenia (SCZ). We will develop data-driven
computational approaches to identify genetic biases towards anatomically connected functional
brain circuits. Aim 2. Experimentally test the identified circuits in several mouse models of ASD
and SCZ. Functional circuits identified by the computational approach will be tested using two
independent mouse models of ASD and two models of SCZ. The dynamics of the circuits will be
explored using multi-site photometric imaging. Aim 3. Correlate mutation biases towards brain
regions, circuits, and cell types with specific ASD phenotypes. Using extensive and deep
phenotypic human data together with genetic data from the same patient cohorts, we will
correlate mutation biases towards brain cell types and circuits with multiple specific ASD
phenotypes.
项目总结
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)
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{{ truncateString('JOSEPH A GOGOS', 18)}}的其他基金
Microcircuit, cellular and molecular dissection of impaired hippocampal function in a mouse model of the 22q11.2 deletion
22q11.2 缺失小鼠模型海马功能受损的微电路、细胞和分子解剖
- 批准号:
10441594 - 财政年份:2020
- 资助金额:
$ 80.32万 - 项目类别:
Discovery and analysis of brain circuits and cell types affected in autism and schizophrenia
发现和分析受自闭症和精神分裂症影响的大脑回路和细胞类型
- 批准号:
10673200 - 财政年份:2020
- 资助金额:
$ 80.32万 - 项目类别:
Microcircuit, cellular and molecular dissection of impaired hippocampal function in a mouse model of the 22q11.2 deletion
22q11.2 缺失小鼠模型海马功能受损的微电路、细胞和分子解剖
- 批准号:
10643829 - 财政年份:2020
- 资助金额:
$ 80.32万 - 项目类别:
Microcircuit, cellular and molecular dissection of impaired hippocampal function in a mouse model of the 22q11.2 deletion
22q11.2 缺失小鼠模型海马功能受损的微电路、细胞和分子解剖
- 批准号:
10241386 - 财政年份:2020
- 资助金额:
$ 80.32万 - 项目类别:
Microcircuit, cellular and molecular dissection of impaired hippocampal function in a mouse model of the 22q11.2 deletion
22q11.2 缺失小鼠模型海马功能受损的微电路、细胞和分子解剖
- 批准号:
10044137 - 财政年份:2020
- 资助金额:
$ 80.32万 - 项目类别:
Discovery and analysis of brain circuits and cell types affected in autism and schizophrenia
发现和分析受自闭症和精神分裂症影响的大脑回路和细胞类型
- 批准号:
10264058 - 财政年份:2020
- 资助金额:
$ 80.32万 - 项目类别:
Deciphering the role of histone methyltransferase SETD1A in schizophrenia susceptibility
破译组蛋白甲基转移酶 SETD1A 在精神分裂症易感性中的作用
- 批准号:
9288683 - 财政年份:2017
- 资助金额:
$ 80.32万 - 项目类别:
The role of GABA-mimetic metabolites in neurodevelopmental and neuropsychiatric d
GABA 模拟代谢物在神经发育和神经精神疾病中的作用
- 批准号:
8675291 - 财政年份:2013
- 资助金额:
$ 80.32万 - 项目类别:
The role of GABA-mimetic metabolites in neurodevelopmental and neuropsychiatric d
GABA 模拟代谢物在神经发育和神经精神疾病中的作用
- 批准号:
8492293 - 财政年份:2013
- 资助金额:
$ 80.32万 - 项目类别:
Mechanisms underlying the functional connectivity deficit in the 22q11 microdelet
22q11 微缺失功能连接缺陷的潜在机制
- 批准号:
8881316 - 财政年份:2012
- 资助金额:
$ 80.32万 - 项目类别:
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