Synaptic Plasticity and Synchrony in the Anterior Cingulate Cortex Circuitry: A Neural Network Approach to Causality of Chronic Visceral Pain and Associated Cognitive Deficits
Synaptic Plasticity and Synchrony in the Anterior Cingulate Cortex Circuitry: A Neural Network Approach to Causality of Chronic Visceral Pain and Associated Cognitive Deficits
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DOI：
10.1007/978-3-319-94593-4_8
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Li, Ying
中科院分区：
文献类型：
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作者：
Li, Ying
人脑影像学研究表明，功能性肠病（如肠易激综合征（IBS））患者的皮层神经元网络在感知疼痛中的重要性，内脏过敏（VH）大鼠的前扣带回（ACC）对结直肠扩张的反应增强。电生理记录显示VH大鼠内侧丘脑（MT）-ACC突触的局部场电位（LFP）的持久增强。在正常大鼠中，MT中的Theta爆发刺激可靠地诱导MT-ACC通路中的长时程增强（LTP），但在VH状态下被阻断。此外，重复强直MT增加ACC神经元的活动和内脏痛反应的正常大鼠，模仿VH大鼠。这些数据提供了决定性的证据，慢性内脏痛与ACC回路中突触可塑性的改变有关。ACC突触强化可能参与了与电刺激激活的信号转导通路相同的信号转导通路，并作为功能性内脏痛的一个有吸引力的细胞模型。利用大鼠赌博任务（RGT），我们发现VH大鼠的决策行为受损。电生理研究显示VH大鼠基底外侧杏仁核（BLA）-ACC突触的LTP减少。多电极阵列记录自由行为大鼠的局部场电位（LFP）显示，慢性内脏痛导致ACC尖峰时间和BLA局部θ振荡中断。最后，交叉相关分析显示，VH与抑制BLA和ACC之间的θ振荡同步，表明这两个区域之间的神经元通信减少。这些数据表明，BLA-ACC神经回路的功能障碍可能是慢性疼痛状态下决策缺陷的相关原因。内脏感觉是一种不依赖于任何外部感觉的感知能力，但其作用是影响引起的行为反应。临床上，迷走神经刺激（VNS）已显示出几种有益的情绪增强效果。我们最近的研究表明，VNS有助于决策，并揭示了VNS在调节LFP和尖峰相位，以及增强与认知性能相关的关键脑区之间的尖峰相位一致性方面的几个重要作用。可以想象，内脏疼痛体验可能更好地解释为疼痛的生物心理社会模型，并反映在神经元结构的矩阵中。对ACC网络中的抑郁和认知缺陷的理解可能为慢性内脏疼痛相关的衰弱性情绪、焦虑和认知障碍提供令人兴奋和强大的未来治疗。
Human brain imaging studies have demonstrated the importance of cortical neuronal networks in the perception of pain in patients with functional bowel disease such as irritable bowel syndrome (IBS).Studies have identified an enhanced response in the anterior cingulate cortex (ACC) to colorectal distension in viscerally hypersensitive (VH) rats. Electrophysiological recordings show long-lasting potentiation of local field potential (LFP) in the medial thalamus (MT)-ACC synapses in VH rats. Theta burst stimulation in the MT reliably induced long-term potentiation (LTP) in the MT-ACC pathway in normal rats, but was occluded in the VH state. Further, repeated tetanization of MT increased ACC neuronal activity and visceral pain responses of normal rats, mimicking VH rats. These data provide conclusive evidence that chronic visceral pain is associated with alterations of synaptic plasticity in the ACC circuitry. The ACC synaptic strengthening may engage signal transduction pathways that are in common with those activated by electrical stimulation, and serve as an attractive cellular model of functional visceral pain.Evidences have shown that most patients with IBS have psychiatric comorbidity. Using rat gambling task (RGT), we discovered an impairment of decision-making behavior in VH rats. Electrophysiological study showed a reduction of LTP in the basolateral amygdala (BLA)-ACC synapses in VH rats. Multiple-electrode array recordings of local field potential (LFP) in freely behaving rats revealed that chronic visceral pain led to disruption of ACC spike timing and BLA local theta oscillation. Finally, cross-correlation analysis revealed that VH was associated with suppressed synchronization of theta oscillation between the BLA and ACC, indicating reduced neuronal communications between these two regions. These data suggest that functional disturbances in BLA-ACC neural circuitry may be relevant causes for the deficits in decision-making in chronic pain state.The viscero-sensation is a faculty of perception that does not depend upon any outward sense, but acts to influence the elicited behavioral response. Clinically, vagus nerve stimulation (VNS) has shown several beneficial effects for mood enhancement. Our recent study characterized that VNS facilitates decision-making and unveiled several important roles for VNS in regulating LFP and spike phases, as well as enhancing spike-phase coherence between key brain areas involved in cognitive performance.It is conceivable that the visceral pain experience may be better explained as a biopsychosocial model of pain and reflected in a matrix of neuronal structures. Understanding of desynchrony in the ACC network and cognitive deficits is likely to provide exciting and powerful future treatment for chronic visceral pain related debilitating mood, anxiety, and cognitive disorders.