Department of Anesthesiology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Sci Adv. 2024 Aug 16;10(33):eadn6272. doi: 10.1126/sciadv.adn6272.
Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.
慢性瘙痒常与焦虑症状并存，形成瘙痒-焦虑共病的恶性循环，难以治疗。然而，慢性瘙痒中焦虑共病的神经元回路机制仍不清楚。在这里，我们报告了慢性瘙痒小鼠模型中的焦虑样行为，并确定了外侧隔核（LS）中的γ-氨基丁酸释放（GABAergic）神经元是慢性瘙痒引起焦虑的关键因素。此外，慢性瘙痒伴随着丘脑核 reunions（Re）投射到 LS GABAergic 神经元的兴奋性投射的增强活动和突触可塑性。选择性化学遗传抑制 Re→LS 回路显著缓解了慢性瘙痒引起的焦虑，而对束缚应激引起的焦虑没有影响。最后，外侧下丘脑（LH）中的 GABAergic 神经元受到 LS GABAergic 神经元的单突触抑制，以介导慢性瘙痒引起的焦虑。这些发现强调了 Re→LS→LH 通路在调节与慢性瘙痒相关的焦虑样共病症状中的潜在意义。
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