【作者】 刘富鑫；

【导师】 罗建红；

【作者基本信息】 浙江大学 ， 神经生物学， 2010， 博士

【摘要】 海马在空间记忆以及新记忆形成中起到重要的作用。最近,越来越多的证据表明海马也可能参与了药物成瘾的过程。因此,海马似乎是联系药物成瘾与学习记忆的重要的关联脑区。理论以及实验研究发现海马神经网络中不同频率的振荡运动,及其独特的发放模式在神经信息编码中扮演着重要的角色。这里,我们使用在体多通道神经信号记录系统,可以在动物清醒活动状态下记录海马CA1神经信息的编码,包括theta波(4-10Hz)和gamma波(40-100Hz)的相位关系,以及theta波和gamma波对CA1区不同神经元的调制。我们发现小鼠海马CA1局部场电位,以及单位放电模式在慢性吗啡处理后发生明显改变。吗啡处理后theta波的能量明显升高,同时在小鼠不同活动状态下theta波的锋频率也发生明显的移动。而且通过研究theta波和gamma波的相位关系发现,theta波和gamma波的相位也发生了移动,并且gamma波的锋频率也明显升高。但是有趣的是,gamma波的能量却没有明显改变。此外,我们也发现在吗啡处理后,锥体神经元与theta波的相位关系发生了移动,而在gamma波中的相位并未改变。而中间神经元与gamma波的相位关系有明显改变,在theta波中的相位却没有改变。为了进一步研究在慢性吗啡处理后影响海马CA1神经信息编码的可能因素,我们通过海马CA1内微注射技术,发现上面的神经信息编码的改变可以被多巴胺受体1的拮抗剂SCH23390明显抑制,而注射多巴胺受体2的拮抗剂以及吗啡受体拮抗剂纳洛酮并没有作用。我们的实验表明海马CA1神经信息编码模式在慢性吗啡处理中的改变参与了药物成瘾,并且这些神经发放模式的改变受海马内多巴胺调控。更多还原

【Abstract】 The hippocampus plays an important role in the formation of new memories and spatial navigation. Recently, growing evidence supports the view that it is also involved in addiction to opiates and other drugs. Theoretical and experimental studies suggest that hippocampal neural-network oscillations at specific frequencies and unit firing patterns reflect information of learning and memory encoding. Here, using multichannel recordings from the hippocampal CAl area in behaving mice, we investigated the phase correlations between the theta (4-10 Hz) and gamma (40-100 Hz) oscillations, and the timing of spikes modulated by these oscillations. Local field potentials and single unit recordings in CAl area of mice receiving chronic morphine treatment revealed that the power of the theta rhythm was strongly increased, at the same time, the theta frequency during different behavioral states shifted markedly, and the characteristic coupling of theta and gamma oscillations was altered. Surprisingly, though the gamma oscillation frequency changed, its power did not. Moreover, the timing of pyramidal cell spikes relative to the theta rhythm and the timing of interneuron spikes relative to the gamma rhythm showed change during chronic morphine administration. Furthermore, both responses were dependent on local dopamine receptor activation, since they were impaired by a selective D1/D5 receptor antagonist. These results indicate that changes of ensemble activity in the CAl area caused by chronic morphine administration related to drug addiction.更多还原