LONG-TERM POTENTIATION IN DEVELOPING HIPPOCAMPUS

长时程增强(LTP)是突触的持续增加 短暂刺激传入纤维后的强度。在成人中 LTP是学习和学习过程中发生的物理变化的模型 记忆。在未成熟的动物中，LTP也可能是正常发育的基础 大脑对环境变化的敏感性等过程 在“关键时期”和病理过程中，如癫痫的发生。 与成年动物不同，发育中的动物经历快速成熟 对LTP的发生至关重要的神经元件的变化。因此， LTP在发育过程中的机制可能与 成年人。本研究旨在阐明长时程增强的作用机制。 发育中的海马体。 1-20天大鼠海马脑片的细胞外记录 将被用来提供LTP发育期的详细调查 有三条通路：穿通径-齿状回，苔藓纤维-CA3； 连合性/关联性CA3。关键的发展阶段和途径 已确定的将使用选择性封锁进行NMDA依赖测试 NMDA或非NMDA受体。细胞内录音将被用于 进一步研究EPSP和EPSP增强的细胞机制 放电阈值的变化(E-S增强)。短期内的变化 将使用细胞外监测的配对来检查抑制效果 脉冲抑制和细胞内记录的斜率电导变化 非增强刺激后的IPSP。中国的长期变化 抑制的可塑性将通过细胞内测量来评估 LTP诱导后IPSP的变化。钙的作用将是 突触后钙离子螯合及激活和抑制的检测 钙依赖的蛋白激酶。最后，中国的发展变化 NMDA受体分布和PKC激活与LTP相关 使用定量放射自显影进行研究。 这项对未成熟动物LTP的系统研究是基于 在成人身上表现良好的机制，有望产生新的 关于发育过程中突触可塑性的信息。

Long-term potentiation (LTP) is the sustained increase in synaptic strength that follows brief stimulation of afferent fibers. In adult animals, LTP is a model of the physical changes that occur in learning and memory. In immature animals, LTP may also underlie normal developmental processes such as the brain's susceptibility to environmental modification during "critical periods" and pathologic processes such as epileptogenesis. In contrast to adults, developing animals undergo rapid maturational changes in the neural elements crucial for the genesis of LTP. Thus mechanisms of LTP during development may differ considerably from those in adults. The goal of this research is to elucidate mechanisms of LTP in developing hippocampus. Extracellular recordings in hippocampal slices from rats 1-20 days will be used to provide a detailed survey of the developmental onset of LTP in three pathways: perforant path-dentate gyrus; mossy fiber-CA3; commissural/associational CA3. Key developmental stages and pathways thus identified will be tested for NMDA-dependence using selective blockade of NMDA or non-NMDA receptors. Intracellular recordings will be used to further examine the cellular mechanisms of potentiation of the EPSP and changes in the firing threshold (E-S potentiation). Short term changes in inhibitory efficacy will be examined using extracellularly monitored paired pulse depression and intracellularly recorded changes in slope conductance of IPSPs following non-potentiating stimulation. Long-term changes in plasticity of inhibition will be assessed by intracellular measurements of changes in IPSP following LTP induction. The role of calcium will be examined by post synaptic calcium chelation and activation and inhibition of calcium-dependent protein kinases. Finally, developmental changes in NMDA receptor distribution and PKC activation as they relate to LTP will be studied using quantitative autoradiography. This systematic investigation of LTP in immature animals is based on mechanisms well-characterized in adults and is expected to yield novel information about synaptic plasticity during development.