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首页> 外文学位 >Neurophysiological Effects of NMDA Receptor Antagonism in Adolescence vs. Adulthood: EEG as a Translational Tool to Study Schizophrenia.
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Neurophysiological Effects of NMDA Receptor Antagonism in Adolescence vs. Adulthood: EEG as a Translational Tool to Study Schizophrenia.

机译：NMDA受体拮抗作用在青春期与成年期之间的神经生理作用：脑电图作为研究精神分裂症的转化工具。

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摘要

Electroencephalogram (EEG) stands out as a highly translational tool for psychiatric research, yet rodent and human EEG are not typically obtained in the same way. The first goal of this study was to develop a tool to record skull EEG in awake behaving rats in a similar manner to how human EEG are obtained. Using this novel rodent EEG technique, I tested whether acute NMDA receptor (NMDAR) antagonism replicates the effects of acute NMDAR-antagonism in humans, and found a strikingly similar shift in EEG oscillatory power from low to high frequencies in rodents, mimicking the effects reported in humans. After validating the translational potential of this approach, I paired EEG with local field recordings to investigate if a disruption to NMDAR signaling during a critical period of development caused long-lasting alterations in neural oscillations in adulthood. I found that rats exposed to an NMDAR-antagonist during adolescence, a critical period for the development of local and long-range synchrony in the brain, showed decreased gamma (30-50 Hz) synchrony between the medial prefrontal cortex (mPFC) and ventral hippocampus (HP) that was evident after NMDAR-antagonist re-exposure during adulthood. The same treatment given to adult rats did not produce this disruption to long-range synchrony, suggesting that adolescent disruption of NMDA signaling may have more robust long-term effects than a similar adult disruption. Interestingly, we did not find alterations in local oscillatory activity in these regions, suggesting that long-range synchrony may be more sensitive than local synchrony to blockade of NMDAR signaling during adolescence. Given that deficits in long-range coherence are seen in patients with schizophrenia, this manipulation in rodents may prove useful in understanding mechanisms behind this phenomenon. Overall, the experiments presented in this Dissertation provide support for the use of EEG as a cross-species translational tool to study schizophrenia across acute and developmental animal models.
机译：脑电图（EEG）在精神病学研究中是一种高度翻译的工具，但啮齿动物和人的脑电图通常不是以相同的方式获得的。这项研究的第一个目标是开发一种工具，以与获取人脑电图相似的方式记录清醒行为大鼠的颅脑电图。使用这种新颖的啮齿动物脑电图技术，我测试了急性NMDA受体（NMDAR）拮抗作用是否能在人类中复制急性NMDAR拮抗作用，并且发现啮齿动物的EEG振荡力从低频到高频发生了惊人的相似，这与报道的影响相似在人类中。在验证了这种方法的翻译潜力之后，我将EEG与局部现场记录配对，以研究在发育的关键时期对NMDAR信号的干扰是否导致成年人神经振荡的长期改变。我发现，在青春期（大脑中局部和远距离同步发展的关键时期）暴露于NMDAR拮抗剂的大鼠中，额前内侧皮层（mPFC）和腹侧之间的γ（30-50 Hz）同步性降低在成年期NMDAR拮抗剂再次暴露后很明显出现海马（HP）。对成年大鼠进行的相同处理并未对远程同步产生这种破坏，这表明与类似的成年破坏相比，青春期NMDA信号破坏可能具有更强的长期作用。有趣的是，我们未发现这些区域的局部振荡活动发生变化，这表明在青春期，远程同步可能比局部同步对NMDAR信号传导更敏感。鉴于在精神分裂症患者中观察到远距离相干性缺陷，因此在啮齿动物中进行这种操作可能有助于理解这种现象背后的机制。总体而言，本论文中提出的实验为使用脑电图作为跨物种转化工具研究跨急性和发育性动物模型的精神分裂症提供了支持。

著录项

  • 作者

    Sullivan, Elyse M.;

  • 作者单位

    University of Maryland, Baltimore.;

  • 授予单位 University of Maryland, Baltimore.;
  • 学科 Neurosciences.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 162 p.
  • 总页数 162
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 地球物理学;
  • 关键词

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