初级体感皮层编码疼痛感知神经机制
文献类型：学位论文
| 作者 | 包充宇 |
| 答辩日期 | 2023-12 |
| 文献子类 | 博士 |
| 授予单位 | 中国科学院大学 |
| 授予地点 | 中国科学院心理研究所 |
| 其他责任者 | 胡理 |
| 关键词 | 疼痛感知 初级体感皮层 锥体神经元 中间神经元 神经机制 |
| 学位名称 | 理学博士 |
| 学位专业 | 认知神经科学 |
| 其他题名 | The neural mechanisms of pain percention in primar somatosensory cortex |
| 中文摘要 | The encoding process of pain information in the cerebral cortex is crucial for our understanding of the mechanisms underlying pain perception and the discovery of objective indicators of pain. Among them, the primary somatosensory cortex (S1) in the cerebral cortex receives extensive projections from neurons in the spinal cord, brainstem, and thalamus. It plays a key role in generating sensory awareness and processing pain perception. Pyramidal neurons and interneurons in S 1 are involved in pain-induced brain responses and make distinct contributions to the encoding of pain perception. In this study, multiple experimental techniques were employed, including silicon electrode electrophysiological recording, calcium imaging, optogenetic modulation, pharmacological modulation, and animal behavioral tests, aiming to reveal the neural mechanisms underlying the encoding of pain perception in S1，explore the coding of pain perception by different types of neurons in S 1，and provide new evidence for potential targets for analgesia and objective indicators of pain. The study first used laser stimulation to induce heat pain in the rat's plantar surface and electrical stimulation to induce tactile sensation. By using silicon electrode electrophysiological recording, the brain responses in S1 were investigated, and it was found that the encoding patterns of pain perception in S1 were distinct from those of tactile perception. Low-frequency event-related potentials (ERPs) played a role in encoding the location and intensity of pain stimuli, while high-frequency gamma band oscillations (GBOs) were only associated with the intensity of pain stimuli. On the other hand, low-frequency ERPs and high-frequency GBOs in tactile perception were only related to the location of the stimuli. Further analysis of neuronal discharge revealed that pain-induced ERPs and GBOs were highly correlated with the activities of pyramidal neurons and interneurons in S 1，with neurons encoding intensity and spatial location attributes showing higher synchronization with ERPs, while interneurons encoding intensity attributes showed higher synchronization with GBOs. ERPs and GBOs induced by tactile stimuli were primarily associated with the activity of pyramidal neurons encoding location information in S1，with pyramidal neurons encoding location attributes exhibiting the highest synchronization with both ERPs and GBOs. To further investigate the differences in encoding pain perception among different types of neurons in S 1，the study employed free-behavioral calcium imaging to observe and record the response patterns of pyramidal neurons and interneurons in mouse S 1 to laser-induced pain stimuli. The results showed that pyramidal neurons in S1 primarily exhibited stronger responses to location attributes in pain perception, while interneurons primarily exhibited stronger responses to intensity attributes in pain perception. To elucidate the neural mechanisms underlying pain-induced brain responses, the study utilized techniques such as optogenetic modulation, pharmacological modulation, and optrode recordings to investigate the regulatory mechanisms of neurons in S 1 on pain-induced behaviors and brain responses. First, optogenetic modulation was used to selectively activate or inhibit pyramidal neurons and interneurons in mouse S 1，and their effects on nocifensive behaviors, including laser heat pain scores and mechanical pain thresholds, were observed. The results showed that only when interneurons were modulated, changes in nocifensive behaviors were observed, while modulation of pyramidal neurons had no effect on nocifensive behaviors. Subsequently, pharmacological modulation combined with electrophysiological recordings and optogenetics combined with electrophysiological recordings were used to further verify the effects of modulating these two types of neurons on pain-induced brain responses in S 1 .Electrophysiological results showed that the low-frequency ERP component in S1 was jointly regulated by pyramidal neurons and interneurons, while the high-frequency GBO component was only regulated by interneurons. In summary, this study revealed the encoding mechanisms of pain information in S1 and the neural mechanisms by which neurons regulate pain perception and pain-induced brain responses. The findings are consistent with previous research and provide causal evidence for the strong correlation between the activity of interneurons in S1 and GBOs as well as nocifensive behaviors. These findings are of significant importance for further understanding the neural encoding principles of pain perception and developing relevant therapeutic approaches. |
| 英文摘要 | 大脑皮层在加工疼痛信息中的编码过程对我们了解痛觉产生机制，发现疼痛的客观指标至关重要。其中大脑皮层中的初级体感皮层(Primary somatosensory cortex, S1)接收来自脊髓、脑干和丘脑神经元的大量投射，是产生感觉意识、加工疼痛感知的关键脑区。S1中的锥体神经元和中间神经元在疼痛诱发脑响应中扮演重要角色，并对疼痛感知的编码有着不同的贡献。本研究采用多种实验技术进行研究，包括硅电极电生理记录、钙离子荧光成像、光遗传学调控、药物调控和动物行为学检测，旨在揭示S1编码疼痛感知的神经机制，探索S1不同神经元对疼痛感知的编码，并为镇痛的潜在靶点与疼痛的客观指标提供了新的证据。 研究首先对大鼠足底使用激光刺激诱发热痛，使用电刺激诱发触觉。通过硅电极电生理记录其s1脑响应发现，s1中疼痛感知的编码模式与触觉感知截然不同。低频事件相关电位(Event-related potentials, ERPs)在疼痛刺激的位置和强度编码中起到作用，而高频伽马振荡(Gamma band oscillations, GBOs)仅与疼痛刺激的强度有关;而触觉的低频ERPs与高频GBOs都仅与刺激的位置有关。进一步计算神经元放电的结果显示，疼痛诱发的ERPs和GBOs主要与S1的锥体神经元和中间神经元活动高度相关，其中编码强度和空间位置属性的神经元活动与ERPs同步性较高，而编码强度属性的中间神经元活动与GBOs同步性较高;触觉诱发的ERPs和GBOs则主要与S1中编码位置信息的锥体神经元活动有关，编码位置属性的锥体神经元与ERPs与GBOs的同步性都最高。 为了进一步探究s1不同类别神经元对疼痛感知编码的差异，研究利用自由活动钙成像记录手段观测并记录了小鼠s1中锥体和中间神经元对激光诱发疼痛束d激的响应模式。结果显示，s1中的锥体神经元主要对疼痛感知中的位置属性有更强的响应，而中间神经元主要对疼痛感知中的强度属性有更强的响应。 为了揭示疼痛诱发脑响应的神经特异性机制，研究利用光遗传学调控，药理学调控和光电极等实验手段来探究s1中神经元对疼痛诱发行为及脑响应的调控机制。首先通过光遗传调控分别激活或抑制小鼠s1中的锥体神经元与中间神经元，观察其对动物疼痛行为包括激光热痛评分与机械痛阂。结果表明，只有在调控中间神经元时，动物的疼痛行为发生了变化，而锥体神经元的调控则对动物疼痛行为没有影响。然后使用药物调控结合电生理记录以及光遗传结合电生理记录实验进一步验证了调控这两种神经元对s1疼痛诱发脑响应的影响。电生理结果显示，s1中的低频ERPs成分受到锥体神经元和中间神经元的共同调控，而高频GBOs成分仅受到中间神经元的调控。 综上所述，这项研究揭示了s1对疼痛信息的编码方式，以及其中神经元调控疼痛感知和疼痛诱发脑响应的神经机制。研究结果既与以往研究具有一致性，又通过因果性的研究验证了s1的中间神经元活动与GBOs及疼痛行为的高度相关。这些发现对于进一步理解疼痛感知的神经编码原理并开发相关治疗方法具有重要意义。 |
| 语种 | 中文 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/46601]  |
| 专题 | 心理研究所_健康与遗传心理学研究室 |
| 推荐引用方式 GB/T 7714 | 包充宇. 初级体感皮层编码疼痛感知神经机制[D]. 中国科学院心理研究所. 中国科学院大学. 2023. |
入库方式： OAI收割
来源：心理研究所
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