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Experience-dependent plasticity of synaptic structure

突触结构的经验依赖性可塑性

基本信息

批准号：
8251352
负责人：
WENBIAO GAN
金额：
$ 2.35万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8251352
关键词：
Adult Animals Behavior Behavioral Brain Cerebral cortex Dendritic Spines Development Electroporation Excitatory Synapse Exhibits Fragile X Syndrome Genetic Growth Health Image Imaging Techniques Impaired cognition Impairment Individual Information Storage Label Learning Life Link Mental Retardation Microscopy Morphology Mus Mutant Strains Mice Neurodevelopmental Disorder Neurons Performance Pharmaceutical Preparations Phase Plastics Play Proteins Pyramidal Cells Regulation Rett Syndrome Role Sensory Sensory Deprivation Shapes Staging Structure Synapses Synaptic plasticity Techniques Testing Time Transgenic Mice Vertebral column base cell type density experience hippocampal pyramidal neuron in utero in vivo insight motor learning motor skill learning mouse model neural circuit novel novel strategies postnatal postsynaptic research study response sensory cortex sensory stimulus skills treatment strategy two-photon young adult

项目摘要

DESCRIPTION (provided by applicant): The aim of this proposal is to study the developmental regulation of dendritic spine plasticity and the role of experience in modifying synaptic connections in postnatal life. Using an in vivo transcranial two-photon imaging technique, changes of individual dendritic spines will be followed over extended periods of time in different cell types and in diverse cortical regions. We will determine how and to what degree sensory experience and learning modulate dendritic spine plasticity in the developing and adult cortex. Furthermore, we will investigate whether experience-dependent spine plasticity is compromised in mouse models of Fragile X syndrome and Rett syndrome and if so, whether drug treatment can restore experience-dependent spine plasticity in mutant mice. Together, these studies will provide fundamental insights into how experience and genetic factors shape neural circuits at different stages of life and suggest new strategies for the treatment of mental retardation. PUBLIC HEALTH RELEVANCE: The aim of this proposal is to study the developmental regulation of synaptic plasticity and the roles of sensory experience and motor learning in modifying neuronal connectivity in postnatal life. By taking advantage of in vivo two-photon microscopy, we will determine changes in postsynaptic dendritic spines in response to novel sensory stimuli and skill learning in the living mouse cortex. We will also establish an important link between abnormal dendritic spine dynamics and aberrant circuit formation in mouse models of mental retardation. These studies will reveal how sensory inputs and learning shape neuronal connectivity in the cerebral cortex at different stages of an animal's life and suggest novel strategies for the treatment of mental retardation.

描述（由申请人提供）：本提案的目的是研究树突棘可塑性的发育调节以及经验在改变出生后突触连接中的作用。使用体内经颅双光子成像技术，将在较长时间内跟踪不同细胞类型和不同皮质区域中个体树突棘的变化。我们将确定感官体验和学习如何以及在多大程度上调节发育中和成人皮层的树突棘可塑性。此外，我们将研究脆性 X 综合征和雷特综合征小鼠模型中经验依赖性脊柱可塑性是否受到损害，如果是的话，药物治疗是否可以恢复突变小鼠中经验依赖性脊柱可塑性。总之，这些研究将为经验和遗传因素如何在生命的不同阶段塑造神经回路提供基本见解，并提出治疗精神发育迟滞的新策略。公共健康相关性：本提案的目的是研究突触可塑性的发育调节以及感觉体验和运动学习在改变产后生活中神经元连接中的作用。通过利用体内双光子显微镜，我们将确定突触后树突棘响应活体小鼠皮层新的感觉刺激和技能学习的变化。我们还将在精神发育迟滞小鼠模型中建立异常树突棘动力学与异常回路形成之间的重要联系。这些研究将揭示动物生命不同阶段的感觉输入和学习如何塑造大脑皮层的神经元连接，并提出治疗精神发育迟滞的新策略。