NEUROTROPHIN MODULATION OF SYNAPTIC STRUCTURE

大脑改变信息处理的能力， 突触连接的结构和强度对于 生物体的成功发育和生存。有 越来越多的证据表明，中枢神经系统利用一些 在发育期和成年期都有相同的分子机制 可塑性。神经营养因子是一类信号分子 促进不同神经元的生长和存活 在神经系统发育的过程中。我们 以前的工作表明，两种神经营养因子，BDNF和NT-3， 而不是NGF，可以迅速增强CA 1区的突触传递 成年大鼠海马区。 一个尚未解答的问题 海马突触传递的快速变化 伴随着或跟随着结构突触的变化， 成年动物许多发展研究的结果强调， 神经营养素作为信号的巨大潜力， 神经元和突触发生期间的形态变化。我们现在 建议检查急性和长期神经营养素的影响， 暴露对成年大鼠神经元和突触形态的影响 海马神经元迄今为止，大多数研究都依赖于 用神经营养素治疗的组织的回顾性检查，或 一种已知能改变突触传递的药剂我们 将使用双光子扫描激光显微镜检查动态 突触结构的变化期间和之后的时期 神经营养因子暴露。为了研究长期的影响， 神经营养因子或Trk受体过表达对突触可塑性的影响， 我们将使用含有这些cDNA的腺病毒（Ad）载体， proteins.我们将腺病毒-神经营养因子载体注射到海马 体外组织（切片）和体内组织。我们将研究各种 突触传递的测量，突触结构和动物 行为为了进一步阐明神经营养因子 在可塑性方面，我们还将使用显性负性Trk构建体， 测试对突触或行为可塑性的影响。

The ability of the brain to alter information processing by changing the structure and strength of synaptic connections is essential for the successful development and survival of organisms. There is increasing evidence that the central nervous system utilizes some of the same molecular mechanisms during both developmental and adult plasticity. The neurotrophins are a class of signalling molecules that promote the growth and survival of distinct neuronal populations during the development of the nervous system. Our previous work demonstrated that two neurotrophins, BDNF and NT-3, but not NGF, can rapidly enhance synaptic transmission in the CA1 region of the adult rat hippocampus. An as yet unanswered question is whether the rapid changes in hippocampal synaptic transmission are accompanied or followed by structural synaptic changes in the adult animal. The results of many developmental studies highlight the enormous potential of the neurotrophins as signals which promote morphological changes during neuro- and synaptogenesis. We now propose to examine the effects of acute and long-term neurotrophin exposure on neuronal and synaptic morphology in living adult rat hippocampal neurons. To date, most studies have relied on retrospective examination of tissue treated with a neurotrophin or a pharmacological agent known to alter synaptic transmission. We will use two-photon scanning laser microscopy to examine dynamic changes in synaptic structure during and following the period of neurotrophin exposure. To examine the long-term effects of neurotrophin or Trk receptor overexpression on synaptic plasticity, we will use adenovirus(Ad) vectors containing cDNAs for these proteins. We will inject Ad-neurotrophin vectors into hippocampal tissue in vitro (slices) and in vivo. We will examine a variety of measures of synaptic transmission, synaptic structure and animal behavior. To further address the involvement of the neurotrophins in plasticity, we will also use dominant negative Trk constructs to test for effects on synaptic or behavioral plasticity.