海马环路中的组合突触可塑性与大鼠情绪研究
文献类型：学位论文
| 作者 | 温菲 |
| 学位类别 | 硕士 |
| 答辩日期 | 2010-10 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 徐林 |
| 关键词 | 海马 长时程增强 长时程抑制 组合可塑性 微小兴奋性突触后电流 社交隔离 性经历 焦虑 抑郁 超声波 |
| 中文摘要 | 海马在某些类型的学习和记忆中起着关键的作用，而突触可塑性（synaptic plasticity）为学习和记忆的模型提供了理论基础。在海马环路中，分布着各种类型的可塑性，包括突触特异的Hebbian形式的可塑性，如长时程增强（long-term potentiation，LTP）和长时程抑制（long-term depression，LTD）；稳态可塑性（homeostatic plasticity），如突触缩放（synaptic scaling）。稳态可塑性是一种整体的调控过程，它可以调节神经元甚至神经网络的平衡；而Hebbian可塑性则是突触特异的，即每个突触进行单独调控的过程。 越来越多的研究提示稳态可塑性和Hebbian可塑性之间存在着空间间隙（spatial gap），那么，如何使得神经元可以通过Hebbian可塑性的过程来维持细胞整体的兴奋性就变得尤为重要。一些报道揭示了LTP和LTD可以在同一突触通路中同时被激活，因此，我们提出组合突触可塑性的概念，即LTP和LTD的组合，它在赋予系统灵活动的同时又可以降低噪音维持系统的稳定性。基于此，本文将围绕这个问题而开展实验工作。 通过对海马CA1区锥体神经元的微小兴奋性突触后电流（miniature excitatory synaptic current, mEPSC）进行测定分析，我们发现mEPSC的幅度分布符合双峰正态分布（double-peak normal distribution）。Theta节律刺激（theta burst stimuli, TBS）诱导后，mEPSC的幅度分布发生改变，呈现右移趋势。随后，采用干扰肽Pep-A2特异地阻断LTP而不影响LTD，我们发现Pep-A2不影响基础状态下mEPSC的幅度分布。在干扰肽Pep-A2存在下，TBS诱导对基础状态下mEPSC的幅度分布也没有影响。结果为揭示LTP和LTD的组合可塑性提供了初步的证据，对进一步理解记忆的编码过程提供了一定的基础。 社交隔离可以引起实验大鼠产生焦虑样和抑郁样的行为，而性经历可以改变动物的情绪状态，降低焦虑样和抑郁样的反应。然而，性经历后进行社交隔离对大鼠情绪的影响并没有报道。在这部分工作中，雄性大鼠经历一周的社交活动（male-male paired housing）或者性活动（male-female paired housing），随后进行一段时间的隔离（1天，2天或者7天）。我们发现，经历过性活动的大鼠，无论隔离与否都表现出相似的情绪反应，包括焦虑样和抑郁样行为以及超声波（ultrasonic vocalizations，USVs）发放；而未经历过性活动的大鼠，其情绪反应随着隔离时间的不同而不同。这一现象提示我们，先前的性经历可以对抗实验动物对环境应激事件，如社交隔离的反应。 |
| 英文摘要 | The hippocampal network plays critical roles in certain types of learning and memory. Synaptic plasticity provides the basis for most models of learning and memory in neural circuits. There are multiple forms of plasticity in the hippocampal circuitry, including synapse-specific Hebbian forms of plasticity, e.g. long-term potentiation (LTP) and depression (LTD), homeostatic plasticity, such as synaptic scaling. Homeostatic plasticity is a global process that regulates overall levels of neuronal and network activity while synapses are modified independently in Hebbian plasticity. Studies on Hebbian and homeostatic plasticity give us a hint that there is a spatial gap. Accordingly, it is important to address whether and how another mechanism exists to maintain an appropriate level of total excitation, as well as allow it to be distributed in different ways across the synapses of a network by Hebbian processes. Some findings also indicate that LTP and LTD are activated at the same time in the same synaptic pathway. Thus, we propose combinatorial plasticity, in combination of LTP and LTD, to protect from lasting effects of noise and endow the system with flexibility and stability. In general, combinatorial plasticity is endowed with homeostatic property via Hebbian processes, and may be required to bridge the spatial gap of synaptic scaling and Hebbian forms of plasticity. In the present study, we find that the distribution of mEPSC amplitudes fit to double-peak Gauss distribution, using blind whole-cell recordings from CA1 pyramidal neurons in acute hippocampal slice. The cumulative fraction of mEPSCrecordings indicates a significant shift in amplitude to the right after TBS induction. Intracellular application of Pep-A2, which specifically interfered with LTP rather than LTD, had no effect on the distribution of mEPSC amplitudes. Meanwhile, TBS induction didn’t alter the distribution of mEPSC amplitudes with intracellular application of Pep-A2. These results may provide a foundation for combinatorial plasticity and further studies on the memory process. Reports on social isolation provided evidence for an enhanced anxiety-like phenotype and depressive-like symptoms, whereas sexual experience could induce significant changes in affective state, decreasing anxiety-like and depressive-like responses. However, it is almost unknown about the behavioral and emotional alterations in male rats treated with isolation after sexual experience. In the present study, we explored anxiety-like and depressive-like parameters as well as USVs emissions in male rats with a period of isolation (control, 1 day, 2 days and 7 days) following 1 week social (male-male paired housing) or sexual (male-female paired housing) interaction. We observed that the pattern of behavioral alterations changed across isolation time in sexually inexperienced rats, while rats with sexual experience exhibited comparable levels of emotionality at each isolation time. These results suggest that prior sexual interaction would counterbalance altered emotional response to environmental stressful stimuli, such as social isolation. |
| 语种 | 中文 |
| 公开日期 | 2010-11-02 |
| 源URL | [http://159.226.149.42:8088/handle/152453/6350]  |
| 专题 | 昆明动物研究所_学习记忆的分子神经机制 |
| 推荐引用方式 GB/T 7714 | 温菲. 海马环路中的组合突触可塑性与大鼠情绪研究[D]. 北京. 中国科学院研究生院. 2010. |
入库方式： OAI收割
来源：昆明动物研究所
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