ACC Sensitization in Visceral Hypersensitive Rats

内脏高敏感性在肠易激综合征(IBS)患者中很常见。前部 扣带回皮质(ACC)是调节对疼痛和肠道运动功能的情感反应的大脑中枢。 人脑成像显示IBS患者ACC对内脏感觉信号的异常处理 然而，其机制尚不清楚。目前的提案旨在描述 ACC神经元的电生理特性及诱导后突触可塑性的探讨 内脏过敏症。我们假设一种增强的内脏传入物质的持续性 伤害性传入ACC诱导以突触增多为特征的ACC神经元可塑性 变速箱。ACC神经元的敏感化可能是由于活动依赖改变的结果 可塑性(长时程增强、长时程增强和长时抑制)。这种高度突触 传递信息会降低痛阈值，放大对疼痛的情感反应。至 为了验证这一假设，我们计划使用两种内脏超敏大鼠模型：结肠过敏反应(鸡蛋 白蛋白)和结直肠刺激(醋酸)。单次ACC神经元棘波的电生理记录 针对结直肠扩张的激发将与反向微透析相结合，直接注入药物 向神经元树突区显示突触谷氨酸能传递的增强。 美国反兴奋剂机构。我们将记录局域场势，并表征LTP的促进和LTD的损失，a 内脏高敏感性启动后，皮质可塑性的关键突触机制。其作用机制 而支持增强的ACC神经元兴奋性和突触可塑性的细胞内信号事件将 被探索。最后，我们将描述ACC在疼痛相关的情感加工中的作用，并阐明 ACC神经元学习记忆诱导的细胞机制。了解 导致ACC神经元可塑性的过程及其在疼痛预期之前的后果 回避行为可能对我们理解中枢神经系统异常的病因和治疗至关重要 与内脏过敏有关。与公共健康的相关性：功能性G1障碍患者 通常表现为内脏过敏。这项研究试图了解原因并提供 治疗这种疾病的线索。

Visceral hypersensitivity is common among patients with irritable bowel syndrome (IBS). The anterior cingulate cortex (ACC) is a brain center which mediates affective responses to pain and gut motor function. Imaging of the human brain indicates abnormal processing of visceral sensory signals by the ACC in IBS patients, however the mechanism is unknown. The current proposal is designed to characterize the electrophysiological properties of ACC neurons, and to explore the synaptic plasticity following the induction of visceral hypersensitivity. We hypothesize that persistence of a heightened tonic visceral afferent nociceptive input to the ACC induces ACC neuronal plasticity characterized by an increase in synaptic transmission. The sensitization of ACC neurons may occur as a result of alteration of activity-dependent plasticity (long-term potentiation, LTP and long-term depression, LTD). This heightened synaptic transmission leads to a reduction in pain threshold and an amplification of affective responses to pain. To test this hypothesis, we plan to use two visceral hypersensitive rat models: colonic anaphylaxis (egg albumin) and colorectal irritation (acetic acid). Electrophysiological recording of single ACC neuronal spike firing in response to colorectal distension will be combined with reversal microdialysis to directly infuse drugs to the dendritic area of neurons to demonstrate the enhancement of synaptic glutamatergic transmission in the ACC. We will record the local field potential and characterize the facilitation of LTP and loss of LTD, a key synaptic mechanism of cortical plasticity, following initiation of visceral hypersensitivity. The mechanisms and intracellular signal events underlying the enhanced ACC neuronal excitability and synaptic plasticity will be explored. Finally, we will characterize the role of ACC in pain-related affective processing and elucidate the cellular mechanisms in the induction of learning and memory in ACC neurons. Understanding the processes that lead to ACC neuronal plasticity and its consequences in pain anticipation that precedes avoidance behavior may prove vital to our understanding of the etiology and treatment of CNS abnormalities associated with visceral hypersensitivity. Relevance to public health: Patients with functional Gl disorders commonly demonstrate visceral hypersensitivity. This study seeks to understand the causes and provide clues for the treatment of this condition.