MORPHOLOGY AND LONG TERM POTENTIATION IN THE HIPPOCAMPUS

这项研究的长期目标是了解神经系统如何 活动改变了大脑中的突触连接， 这种改变的连接性和行为学习之间的关系， 记忆使用联合长时程增强（LTP）作为模型， 了解神经元连接如何随着神经元的模式而变化， 活动的变化，拟议的研究解决的问题，改变 存在的轴棘突触和突触发生与LTP相关， 成年大鼠海马体，一种可能在大脑中占据重要地位的结构， 与心理健康相关的认知功能障碍该系统 研究的是兴奋性内嗅皮层（EC）投射到 海马CA 1区锥体细胞远端树突状簇。分子我们 初步研究表明，成人CA 1区的树突和突触 S.分子l）与轴棘突触共享特征， 齿状回，LTP的形态学相关意味着 现有突触的修改; 2）具有一些意想不到的 形态学特征表明正在进行的树突状生长， 突触发生这些特征包括：丝状伪足;大，静脉曲张 树突棘;棘相关的相对高的概率 多核糖体;锥体细胞树突内陷 树突和轴突;以及树突的无突触突起。这些 正常成人CA 1的形态学观察。分子导致 假设LTP的形态相关性在这里将不同于 这些是以前在其他海马区获得的。具体目标l 表征EC-CA 1突触处LTP的解剖学相关性， 检验LTP与增长相关的假设。 具体目标2表征了EC-CA 1突触的突触学， 并证实了锥体细胞树突 参与在CA 1中观察到的不寻常的形态学相互作用。 分子 具体目标3检验了阻断NMDA 受体，阻止在几个海马LTP的诱导 系统，也可以防止LTP的解剖相关性。具体目标l 3主要采用体外海马脑片制备， EC-CA 1通路的研究比体内研究更明确， 通过：每个锥体的突触数量的体视学测定 功能相关突触特征的量化;以及 连续切片评价和重建生长相关的 形态特征使用顺行示踪剂注射到EC中， 在超微结构水平标记EC-CA 1突触，特异性目的2 决定EC轴突与之突触的突触后成分的类型 在CA 1。金调快速高尔基体法也被用来表征在 在光镜和电镜水平上， 在初步研究中发现。LTP的解剖学相关性 在这里获得的，连同以前的研究，在其他海马 系统，应允许未来的研究，以评估结构变化， 相关的行为学习范式。通过这种方式， 对结构修饰与 认知也会进化。因为海马状突起显然是 在认知中的作用，理解活动依赖性突触修饰 也有助于我们更好地了解海马 功能障碍及其对认知的影响

The long-term objective of this research is to understand how neural activity modifies synaptic connectivity in brain and to understand the relationship between this altered connectivity and behavioral learning and memory. Using associative long-term potentiation (LTP) as a model for understanding how neuronal connectivity changes as the pattern of neural activity changes, the proposed studies address the question of altered existing axospinous synapses and synaptogenesis as correlates of LTP in the adult rat hippocampus, a brain structure that may figure prominently in mental health-related cognitive dysfunction. The system to be investigated is the excitatory entorhinal cortical (EC) projection to the CA1 pyramidal cell distal apical dendritic tuft in s. moleculare. Our preliminary studies indicate that the dendrites and synapses in adult CA1 s. moleculare l) share features with the axospinous synapses in the dentate gyrus, where the morphological correlates of LTP imply the modification of existing synapses; and 2) possess some unexpected morphological features that suggest ongoing dendritic growth and synaptogenesis. These features include: filopodia; large, varicose dendritic spines; a relatively high probability of spine-associated polyribosomes; invaginations of pyramidal cell dendrites by other dendrites and axons; and synapseless protrusions from dendrites. These morphological observations in normal adult CA1 s. moleculare lead to the hypothesis that the morphological correlates of LTP here will differ from those obtained previously in other hippocampal regions. Specific Aim l characterizes the anatomical correlates of LTP at the EC-CA1 synapses to test the hypothesis that LTP correlates with increased growth there. Specific Aim 2 characterizes the synaptology of the EC-CA1 synapses at the electron microscopic level and confirms that pyramidal cell dendrites participate in the unusual morphological interactions observed in CA1 s. moleculare. Specific Aim 3 tests the hypothesis that blocking the NMDA receptor, which prevents the induction of LTP in several hippocampal systems, also prevents the anatomical correlates of LTP. Specific Aims l and 3 principally use the in vitro hippocampal slice preparation, where the EC-CA1 pathway can be studied less ambiguously than in vivo, followed by: stereological determination of the number of synapses per pyramidal cell; quantification of functionally relevant synaptic features; and serial section evaluation and reconstruction of growth-associated morphological features. Using anterograde tracer injections into the EC to label EC-CA1 synapses at the ultrastructural level, Specific Aim 2 determines the types of postsynaptic elements with which EC axons synapse in CA1. The gold-toned rapid Golgi method is also used to characterize at the light and electron microscopic levels the growth-like structures identified in preliminary studies. The anatomical correlates of LTP obtained here, together with previous studies in other hippocampal systems, should allow future studies to evaluate structural changes in hippocampally relevant behavioral learning paradigms. In this way, additional insight into the relationship between structural modification and cognition may evolve. Because the hippocampus apparently plays a key role in cognition, understanding activity-dependent synaptic modification in the hippocampus should also help us to better understand hippocampal dysfunction and its impact on cognition.