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大鼠编码痛觉和触觉信息的脊髓-皮层神经机制
其他题名The neural mechanisms of the spinal cord and cortex in touch and nociception modulation and processing
王夏青
导师胡 理
2022-06
摘要躯体感觉的传导及知觉的形成由脊髓和大脑共同作用完成,同步记录脊髓和大脑对躯体感觉信息的编码过程,对于了解其潜在机制有重要意义。大脑和脊髓同步研究的困难主要来自脊髓,脊髓位置及结构的特殊性对实验技术和实验条件有着更高的要求。因此,以往大多数研究都是在麻醉状态下开展,而清醒状态和麻醉状态的神经元活动存在显著差异,在自由活动的动物中开展进一步研究十分必要。多通道在体电生理记录具有高时间和空间分辨率,且方便应用于动物研究。此外,近年一些基于石墨烯和碳纳米管的柔性神经电极被开发出来,相比于传统的硬质电极,它们在机械依从性、生物相容性及长期稳定性等多方面都展现了巨大优势,也为脊髓研究提供了新的契机。 因此,本研究借助碳纳米管柔性电极开发了一种可实现对自由活动的大鼠脊髓和大脑同步记录的新方法。基于脊髓背角是躯体感觉外周输入的第一个整合部位,初级躯体感觉皮层(Primary somatosensory cortex, S1)接收来自脊髓、脑干和丘脑神经元的大量投射,是感觉意识产生的关键脑区。我们选择脊髓背角和 S1 为目标位置,使用激光痛刺激和低电流电刺激两种模态,验证了这种同步记录方法的有效性;并进一步探索了脊髓和 S1 对痛觉和触觉信息的编码机制。 使用激光痛刺激对这一同步记录方法的验证显示,与以往对脊髓电生理的研究相比,本研究采集到信噪比较高的脊髓电信号。且脊髓和 S1 对痛觉刺激的编码,具体体现在激光刺激后 250~350ms,脊髓场电位出现一个明显的负成分,该成分幅值受刺激强度和位置调控显著。在激光刺激呈现后约 270~350ms,S1-N1 成分出现,且成分幅值和潜伏期均被刺激强度调控。此外,脊髓和 S1 的γ频段振荡信号(gamma-band oscillations,GBOs)及神经元放电率均受刺激强度调控。激光诱发的脊髓和 S1 响应特征相关分析以及瞬时幅值相关分析均证实了脊髓和 S1 的高度共变性。响应特征与疼痛行为评分相关分析发现,与 S1 相一致,脊髓的场电位幅值和 GBOs 也与动物疼痛行为评分存在高相关。此外,因果连接分析发现,在 0-300Hz 频段,存在显著的脊髓向 S1 方向的信息流动,这可能是脊髓向 S1 传递激光刺激特征信息的重要证据。简单来说,脊髓和 S1 对痛觉的编码特征虽然存在一些差异,但整体而言,无论是表征物理刺激特征,还是反映疼痛体验,脊髓和 S1 都具有较高的相似性和一致性。 脊髓和 S1 对电刺激触觉信息的响应,具体表现在刺激后 20~30ms,脊髓场电位出现一个明显的负成分,这一成分受刺激强度及刺激位置的调控均不显著;在电刺激呈现后 20~30ms,40~60ms,S1 场电位分别出现一个明显的负成分,两个成分的幅值均受刺激强度调控。此外,脊髓神经元放电率既受电刺激强度的调控,又受刺激位置调控,而 S1 神经元放电率则均不受二者调控。总之,电刺激触觉信息诱发的脊髓和 S1 响应特征差异较大, 且与激光刺激诱发的脊髓和S1 响应特征的高相关所不同,电刺激诱发的相关主要在区域内,且相关特征较少。电刺激诱发的脊髓和 S1 瞬时幅值相关性也较低,因果连接分析显示,无论是脊髓→S1 方向,还是 S1→脊髓方向,均无显著的信息流动。这可能是不同刺激模态编码的差异,但仍需进一步的验证。 综上所述,本研究开发了一种全新的可实现对自由活动的大鼠脊髓-皮层同步记录的实验方法,并以脊髓背角和 S1 为目标位置,分别使用激光刺激和电刺激验证了这一模型的有效性;实验结果既有与已有研究的一致性,又有新结果符合解剖结构的合理性,证实了这种同步记录方法的可行性。同时,也探讨了脊髓和 S1 对痛觉和触觉编码的神经机制,以及脊髓和 S1 的功能连接,为以后开展中枢系统协同研究提供了新方法。
其他摘要The conduction of somatosensory information and the formation of perception are processed by the spinal cord and the brain collaboratively. Simultaneous recording the interactions between the brain and spinal cord is important to reveal the functional connectivity within the entire central nervous system. The biggest challenge during this process is from spinal cord, because unlike brain, the spinal cord flexes with the body during movement. Animal research plays an important role in overcoming the limitations of human study, especially in the mechanism research. The vivo multi- channel recording method has a high temporal and spatial resolution, and can be easily used in animals. Besides, most previous studies have been carried out under anesthesia, and the neuronal activity is significant different between awake and anesthetized states. Therefore, it is necessary to carry out further studies in freely moving animals. In recent years, the soft carbon nanotube fiber (CNTF) electrodes have been developed, showing great advantages over traditional rigid electrodes in mechanical compliance, biocompatibility and long-term stability. Therefore, we developed a new method with CNTF electrodes, to record the stimulus-related-signals in spinal cord and brain simultaneously in freely moving rats. The spinal dorsal horn is the first integrated site of somatosensory peripheral input. The primary somatosensory cortex (S1) is the key brain region for sensory consciousness, which receives a large number of projections from spinal cord, brainstem and thalamus. Thus, we set spinal dorsal horn and S1 as target sites and validated this synchronous recording methods using laser and electrical stimulus. Our present study has a higher signal-to-noise ratio (SNR), compared with previous spinal cord related studies. In the time interval 250~350ms after laser stimulus onset, there is a negative component in spinal cord field potential, the amplitude of this component is regulated by stimulus intensity and location significantly. The amplitude increases with stimulus intensity, and the amplitude on the ipsilateral side is significantly higher than the contralateral side. The S1-N1 appears about 270~350ms after the onset of laser stimulus, and both the latency and amplitude of S1-N1 are regulated by stimulus intensity. Besides, both the γ-oscillations (gamma-band oscillations, GBOs) and the neuron firing rate in spinal cord and S1 are regulated by the stimulus intensity significantly. The correlation analysis shows a high correlation between spinal cord and S1. In addition, the spinal cord response characteristics evoked by laser are highly correlated with pain score, which is consistent with the relationship in S1. This indicates that spinal cord electrophysiological signals may also represent pain intensity. In the end, we further applied normalized partial directed coherence (nPDC) analysis to the electrophysiological signal in spinal cord and S1, and find an increased information flow from spinal cord to S1 during laser stimulus presentation in 0-300Hz band, and the information flow increases with stimulus intensity. In short, although there are some differences between spinal cord and S1 in pain processing, they show high consistency in demonstrating stimulus physical characteristics and representing pain intensity. In the time interval between 20 and 30ms after electrical stimulus onset, there is a negative component in the spinal cord field potential, which is not regulated significantly by electrical stimulus intensity and location. In addition, at the time interval of 20~30ms and 40~60ms after electrical stimulus onset, there is a negative component in the S1 field potential respectively, both of them are regulated by stimulus intensity. Besides, the spike firing rate in the spinal cord is regulated by stimulus intensity and location, which increases with stimulus intensity, and the firing rate on the ipsilateral side is higher than the contralateral side. While the spike firing rate in S1 neither regulated by stimulus intensity, nor by stimulus location. Collectively, different from the high consistency in laser stimulus modality, there are more difference in electrical modality. The further nPDC analysis shows there is no significant information flow between spinal cord and S1. In conclusion, we developed a novel experimental method for synchronous recording of spinal cord and cortex in freely moving rats, and verified the validity of this method with laser and electrical stimulus. And some of our present results are consistent with previous researches, the new findings are also reasonable in anatomy. Besides, the neural mechanism of spinal cord and S1 in pain and touch modulation and processing, as well as the functional connection between spinal cord and S1 are also explored. And this method can be widely used in future research to explore the underlying neural mechanisms of sensation and motion.
关键词躯体感觉 脊髓背角 初级躯体感觉皮层 柔性神经电极 同步记录
学位类型博士
语种中文
学位名称理学博士
学位专业认知神经科学
学位授予单位中国科学院大学
学位授予地点中国科学院心理研究所
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/43166
专题认知与发展心理学研究室
推荐引用方式
GB/T 7714
王夏青. 大鼠编码痛觉和触觉信息的脊髓-皮层神经机制[D]. 中国科学院心理研究所. 中国科学院大学,2022.
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