Experience-dependent plasticity of synaptic structure

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出生后生活中经验在修改突触连接中的作用。使用体内经颅双光子成像技术，将在不同细胞类型和不同皮质区域中长时间跟踪单个树突棘的变化。我们将确定感觉经验和学习如何以及在何种程度上调节发育和成人皮质中树突棘的可塑性。此外，我们将研究经验依赖性脊柱可塑性是否在脆性X综合征和Rett综合征小鼠模型中受损，如果是这样，药物治疗是否可以恢复突变小鼠的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，并为治疗精神发育迟滞提出新的策略。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调节和感觉经验和运动学习在出生后生活中修改神经元连接的作用。通过利用在体双光子显微镜，我们将确定突触后树突棘的变化，以响应新的感觉刺激和技能学习在活的小鼠皮层。我们也将建立一个重要的联系异常树突棘动力学和异常电路形成的小鼠模型的精神发育迟滞。这些研究将揭示感觉输入和学习如何在动物生命的不同阶段塑造大脑皮层中的神经元连接，并提出治疗精神发育迟滞的新策略。

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.