Role of semaphorin 3A in synaptic transmission in the adult mouse hippocampus.

记忆，指的是生物体整合、编码、存储和回忆信息的能力，是定义经验的基本和适应性过程，由高度专业化的交流地点--突触--的脑细胞之间连接强度的变化来编码。大多数兴奋性突触被安置在称为树突的树突发出的小突起内。树突棘结构和突触分子组成的变化被称为突触可塑性，被认为是学习和记忆形成的神经生物学基础。许多调节突触可塑性的潜在事件显示出与神经发育过程中发生的惊人相似的过程，长期以来的假设是，负责神经发育的分子机制可能也有助于成人神经系统中与学习和记忆相关的可塑性事件。指导线索蛋白是一种高度保守的蛋白质，最初被描述为在胚胎发育期间帮助指导轴突迁移和突触连接，但最近的研究表明，它们可能在塑造成人大脑中的突触传递方面发挥作用。信号素是一类膜结合和分泌的化学排斥引导信号家族，最初被描述为通过作用于肌动蛋白细胞骨架参与排斥细胞反应的关键分子。分泌的引导线索信号素3A(Sema3A)继续在成年海马体中表达，海马体是一种参与学习和空间记忆形成的大脑结构，但对其生理功能知之甚少。本研究旨在探讨Sema3A在成年大鼠海马区空间记忆形成的突触传递和可塑性中的作用，包括：i)检测Sema3A对成年海马兴奋性神经元细胞形态和突触传递的影响；ii)评估Sema3A对经典的活性依赖性突触可塑性的贡献；以及iii)确定Sema3A在空间记忆功能中的贡献。综上所述，这项研究计划将强调在发育过程中重要的指导性线索如何通过对突触的结构和分子组成的影响继续在塑造成人大脑中的突触传递方面发挥关键作用。

Memory, which refers to the ability of organisms to integrate, encode, store, and recall information, is a fundamental and adaptive process that defines experience, and is encoded by changes in the strength of connections between brain cells at highly-specialized sites of communication called synapses. Most excitatory synapses are housed within small protrusions emanating from dendrites called dendritic spines. Changes in both structure of dendritic spines and the molecular composition of synapses, termed synaptic plasticity, are thought to serve as the neurobiological basis of learning and memory formation. Many of the underlying events that regulate synaptic plasticity show a striking similarity to processes that occur during neural development, and it is a long-standing hypothesis that the molecular mechanisms responsible for neural development may also contribute to plasticity events related to learning and memory in the adult nervous system. Guidance cue proteins are highly-conserved proteins that were first described helping to direct axonal migration and synaptic connections during embryonic development, but recent work has suggested that they may play a role in shaping synaptic transmission in the adult brain. Semaphorins are a family of membrane-bound and secreted chemorepulsive guidance cues that were first described as key molecules involved in repulsive cellular responses through actions on the actin cytoskeleton. The secreted guidance cue semaphorin 3A (Sema3A) continues to be expressed in the adult hippocampus, a brain structure involved in learning and spatial memory formation, yet little is known regarding its physiological function. The research program proposed here will investigate the role of Sema3A in synaptic transmission and plasticity underlying spatial memory formation in the adult hippocampus by addressing the following aims: i) Examine the effect of Sema3A on cellular morphology and synaptic transmission in excitatory neurons in the adult hippocampus, ii) Assess the contribution of Sema3A to classic activity-dependent forms of synaptic plasticity, and iii) Determine the contribution of Sema3A in spatial memory function. In summary, this research program will highlight how instructive guidance cues important during development continue to play key roles in shaping synaptic transmission in the adult brain through effects on both the structure and molecular composition of synapses.