基于沉默型突触的海马CA1对感觉信息的表征机制

发布时间：2018-03-05 20:05

本文选题：海马　切入点：感觉信息　出处：《华东师范大学》2017年博士论文　论文类型：学位论文

【摘要】：海马是哺乳动物负责学习与记忆的重要脑区。作为"在线(online)"信息处理系统,在记忆的获取和短期储存过程中,活动依赖的神经可塑性变化在海马环路发生,以存储所经历的事件。目前的观点认为,海马作为多感觉模态的脑区,对感觉信息的处理基于"稀疏编码"这一原则,即某一感觉信息仅有少量海马神经元负责编码。这一稀疏编码的规则在海马处理空间及非空间信息中均被报道。然而,目前对海马稀疏编码感觉信息的细胞及环路机制还不明确。本实验采用在体全细胞膜片钳技术,记录视觉刺激在麻醉和清醒状态下的成年啮齿动物海马CA1锥体细胞诱发的活动,探索感觉信息在海马CA1的表征机制及可能的生理意义。实验发现,麻醉状态下,闪光刺激只能在约30%的CA1锥体细胞上诱发反应,符合前人报道的海马以稀疏编码的方式处理感觉信息。而当膜电位去极化时,正常情况不起反应的细胞均可对闪光刺激发生兴奋性反应。进一步研究发现,这一反应由NMDA(N-methyl-D-aspartate)受体介导,即来源于突触后膜仅装配有 NMDA 受体而无 AMPA(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)受体的沉默型突触。此外,当该闪光刺激和突触后细胞持续去极化配合出现时,可在相应的沉默型突触诱发突触增强,即发生沉默型突触的去沉默化,产生在正常情况下能对闪光刺激能起反应的功能型突触。接下来我们在头清醒固定的成年小鼠上发现,去极化CA1锥体细胞膜电位同样可以使原本没有反应的细胞被闪光刺激诱发出兴奋性反应。而且在麻醉状态下,通过接受特异性投射的方式,不同的视觉刺激在同一个CA1锥体细胞上引起不同的反应。由此我们得到结论,海马CA1锥体细胞上普遍分布的沉默型突触接受广泛且特异性的感觉投射,并介导具有生理意义的潜在反应。这些在大量CA1锥体细胞上存在的、与感觉相关的沉默型突触为海马获取和形成新记忆时发生的可塑性变化提供了空间。
[Abstract]:The hippocampus is an important area of the brain responsible for learning and memory in mammals. As an online information processing system, during the acquisition and short-term storage of memory, activity-dependent neural plasticity changes occur in the hippocampal loop. The current view is that the hippocampus, as a multi-sensory brain region, processes sensory information based on the principle of sparse coding. That is, only a small number of hippocampal neurons encode a certain sensory information. This sparse encoding rule is reported in both spatial and non-spatial information processing by the hippocampus. However, At present, the cell and loop mechanism of the sparse encoding of sensory information in the hippocampus is not clear. In this experiment, whole-cell patch clamp technique was used to record the activities induced by visual stimulation in the hippocampal CA1 pyramidal cells in anesthetized and awake adult rodents. To explore the characterization mechanism and possible physiological significance of sensory information in hippocampal CA1, it was found that under anesthesia, flash stimulation could only induce response on about 30% of CA1 pyramidal cells. In accordance with previous reports, the hippocampus processes sensory information in a sparse coding manner. When the membrane potential is depolarized, the cells that do not respond to normal conditions can develop excitatory responses to flash stimuli. This response was mediated by the NMDAN-methyl-D-aspartatereceptor, that is, the silent synapse from which the postsynaptic membrane had only NMDA receptors and no 伪 -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acidotor. In addition, when the flash stimulation and the continuous depolarization of postsynaptic cells appeared, The synapses can be enhanced at the corresponding silent synapses, that is, the desilencing of the silencing synapses, resulting in functional synapses that normally respond to flash stimuli. Then we found them in adult mice with fixed heads. Depolarization of CA1 pyramidal cell membrane potential can also induce excitatory responses of previously unresponsive cells by flash stimulation, and in anesthetized state, by receiving specific projections, Different visual stimuli cause different responses to the same CA1 pyramidal cells. We conclude that the silent synapses widely distributed in the hippocampal CA1 pyramidal cells receive extensive and specific sensory projections. These sensory silent synapses in a large number of CA1 pyramidal cells provide space for the plasticity of hippocampus to acquire and form new memories.
【学位授予单位】：华东师范大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：Q42

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