Abstract：
Accumulating evidences suggest dysfunctions in the hippocampus are associated with chronic pain. Nevertheless, the role of hippocampal circuitry in pain memories and emotional responses is not yet fully understood. In this study, we utilized a comprehensive approach that combined electromyography (EMG), photochemical genetic techniques, and anxiety-related behavioral paradigms to investigate the involvement of dorsal hippocampus (DH) and ventral hippocampus (VH) in visceral sensitivity and anxiety behaviors in male rats. Our results demonstrated that IBS-like rats exhibited comorbid visceral hypersensitivity and anxiety, along with the number of activated neurons in the VH was higher than that in the DH. Manipulation of glutamatergic neurons in the hippocampus was identified as a crucial mechanism underlying the mediation of both visceral sensitivity and anxiety behaviors. Specifically, optogenetic activation of the DH induced both visceral hypersensitivity and anxiety, while activation of the VH induced anxiety but did not affect visceral sensitivity. Conversely, chemogenetic inhibition of the DH reduced both visceral hypersensitivity and anxiety, whereas inhibition of the VH alleviated anxiety but did not alleviate visceral hypersensitivity in IBS-like rats. Our study highlights the important role of early life stress in inducing visceral hypersensitivity and anxiety, and further elucidates the distinct functional contributions of the DH and VH to these behavioral changes. These findings provide a theoretical basis for the diagnosis and treatment of IBS, and suggest that targeting specific hippocampal neuron subtypes may represent a promising therapeutic approach.
摘要：
越来越多的证据表明海马功能障碍与慢性疼痛有关。然而，海马电路在疼痛记忆和情绪反应中的作用尚未完全了解。在这项研究中,我们采用了一种综合的方法，结合了肌电图(EMG)，光化学遗传技术，和焦虑相关行为范式探讨背侧海马（DH）和腹侧海马（VH）在雄性大鼠内脏敏感性和焦虑行为中的作用。我们的结果表明，IBS样大鼠表现出共病的内脏超敏反应和焦虑，随着VH中激活神经元的数量高于DH中的数量。海马中谷氨酸能神经元的操纵被认为是介导内脏敏感性和焦虑行为的关键机制。具体来说,DH的光遗传学激活诱导内脏高敏感性和焦虑，而VH的激活诱导焦虑，但不影响内脏敏感性。相反，DH的化学遗传抑制降低了内脏高敏感性和焦虑，而抑制VH可减轻IBS样大鼠的焦虑，但不能减轻内脏超敏反应。我们的研究强调了早期生活压力在诱导内脏过敏和焦虑中的重要作用，并进一步阐明了DH和VH对这些行为变化的不同功能贡献。这些发现为IBS的诊断和治疗提供了理论依据,并表明靶向特定的海马神经元亚型可能代表一种有希望的治疗方法。
