Experience-dependent plasticity of synaptic structure

描述(申请人提供)：这项建议的目的是研究树突棘可塑性的发育规律，以及经验在改变出生后生活中突触连接的作用。使用活体经颅双光子成像技术，将在较长的时间内跟踪不同细胞类型和不同皮质区域中单个树突棘的变化。我们将确定感觉体验和学习如何以及在多大程度上调节发育中的和成人皮质中树突棘的可塑性。此外，我们将调查脆性X综合征和Rett综合征小鼠模型中经验依赖型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的经验依赖型脊柱可塑性。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的见解，并为治疗精神发育迟滞提供新的策略。公共卫生相关性：这项建议的目的是研究突触可塑性的发育规律，以及感觉经验和运动学习在改变出生后生活中神经元连接方面的作用。通过利用活体双光子显微镜，我们将确定突触后树突棘在活体小鼠皮质中对新的感觉刺激和技能学习的反应的变化。我们还将在智力低下的小鼠模型中建立树突棘动力学异常和异常回路形成之间的重要联系。这些研究将揭示在动物生命的不同阶段，感觉输入和学习是如何塑造大脑皮层神经元连接的，并为治疗精神发育迟缓提出新的策略。

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.