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首页> 外文学位 >The effect of Ras/MAPK signaling in the mouse hippocampus: A morphological examination of synaptic and dendritic alterations in CA1.
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The effect of Ras/MAPK signaling in the mouse hippocampus: A morphological examination of synaptic and dendritic alterations in CA1.

机译：Ras / MAPK信号传导在小鼠海马中的作用：CA1突触和树突状变化的形态学检查。

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摘要

Considerable evidence has accumulated demonstrating that dendritic processes involved in synaptic plasticity are critical for learning and memory. However, little research has focused on presynaptic mechanisms underling learning and memory in mammals. The laboratory of Dr. Alcino Silva at the University of California at Los Angeles developed a RasG12V mouse model, and conducted experiments which exposed novel aspects of Ras function in post-mitotic neurons, by taking advantage of this mutation to increase signaling through the mitogen-activated protein kinase (MAPK) pathway. This mutant demonstrated enhanced long-term potentiation (LTP), enhanced behavioral learning, and a primarily presynaptic localization of this Ras isomer. The current research examined changes in spine and synaptic morphology that may underlie the types of neural plasticity observed in this mutant. No changes in synapse per neuron densities for total synapses, total macular synapses or total perforated synapses were observed in RasG12V as compared to wild-type (WT) mice. Electron and light microscopy analysis of hippocampal CA1 excitatory terminals revealed that the general appearance of presynaptic terminals, spines, and postsynaptic densities was similar in WT and RasG12V mice. There was however, in the RasG12V mutant, a significant increase in the density of docked vesicles, an increased proportion of concave perforated synapses, and an increased number of mushroom shaped spines. The current research suggests that the presynaptic signaling mechanisms associated with this mutant may modulate neural plasticity by increasing the size of the readily-releasable vesicular pool. However, while alterations in presynaptic vesicular docking may be the initial and primary mechanism underlying the electrophysiological and behavioral alterations in these animals, this change apparently has downstream effects, with an associated increase in the proportion of concave perforated synapses and mushroom spines. Taken together, these alterations in the mutant may account for the enhancements in LTP and learning previously observed, and suggest that alterations in these synaptic and dendritic morphological characteristics may play a critical role in LTP, and, learning and memory processes in general.
机译：积累了大量证据，表明突触可塑性所涉及的树突过程对于学习和记忆至关重要。但是，很少有研究集中在突触前机制作为哺乳动物学习和记忆的基础。加利福尼亚大学洛杉矶分校的Alcino Silva博士实验室开发了RasG12V小鼠模型，并进行了实验，通过利用这种突变来增加有丝分裂原信号，从而揭示了有丝分裂后神经元中Ras功能的新方面。激活的蛋白激酶（MAPK）途径。此突变体表现出增强的长期增强（LTP），增强的行为学习以及该Ras异构体的主要突触前定位。当前的研究检查了脊柱和突触形态的变化，这些变化可能是该突变体中观察到的神经可塑性的基础。与野生型（WT）小鼠相比，在RasG12V中未观察到总突触，总黄斑突触或总穿孔突触的每个神经元密度的突触变化。对海马CA1兴奋性终末的电子和光学显微镜分析表明，野生型和RasG12V小鼠的突触前终末，棘和突触后密度的总体外观相似。但是，在RasG12V突变体中，对接囊泡的密度显着增加，凹孔突触的比例增加，蘑菇状棘突数量增加。当前的研究表明，与该突变体相关的突触前信号传导机制可能通过增加易于释放的囊泡池的大小来调节神经可塑性。然而，虽然突触前囊泡对接的改变可能是这些动物电生理和行为改变的基础和主要机制，但这种改变显然具有下游作用，伴随着凹孔突触和蘑菇刺的比例增加。综上所述，突变体中的这些改变可能解释了LTP和先前观察到的学习的增强，并表明这些突触和树突形态特征的改变可能在LTP中以及整个学习和记忆过程中起着关键作用。

著录项

  • 作者

    LeBoutillier, Janelle Catherine.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Psychology Psychobiology.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 162 p.
  • 总页数 162
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 心理学;
  • 关键词

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