Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, Gothenburg, Sweden.
Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Biol Psychiatry. 2022 Nov 1;92(9):709-721. doi: 10.1016/j.biopsych.2022.04.020. Epub 2022 May 18.
Anxiety disorders are associated with an altered perception of the body's internal state. Therefore, understanding the neuronal basis of interoception can foster novel anxiety therapies. In rodents, the feeding status bidirectionally modulates anxiety-like behavior but how the sensing of gastrointestinal state affects anxiety remains unclear.
We combined chemogenetics, neuropharmacology, and behavioral approaches in male and female rats to test whether vagal afferents terminating in the gastrointestinal tract mediate feeding-induced tuning of anxiety. Using saporin-based lesions and transcriptomics, we investigated the chronic impact of this gut-brain circuit on anxiety-like behavior.
Both feeding and selective chemogenetic activation of gut-innervating vagal afferents increased anxiety-like behavior. Conversely, chemogenetic inhibition blocked the increase in anxiety-like behavior induced by feeding. Using a selective saporin-based lesion, we demonstrate that the loss of gut-innervating vagal afferent signaling chronically reduces anxiety-like behavior in male rats but not in female rats. We next identify a vagal circuit that connects the gut to the central nucleus of the amygdala, using anterograde transsynaptic tracing from the nodose ganglia. Lesion of this gut-brain vagal circuit modulated the central amygdala transcriptome in both sexes but selectively affected a network of GABA (gamma-aminobutyric acid)-related genes only in males, suggesting a potentiation of inhibitory control. Blocking GABAergic signaling in the central amygdala re-established normal anxiety levels in male rats.
Vagal sensory signals from the gastrointestinal tract are critical for baseline and feeding-induced tuning of anxiety via the central amygdala in rats. Our results suggest vagal gut-brain signaling as a target to normalize interoception in anxiety disorders.
焦虑症与对身体内部状态的感知改变有关。因此，了解内脏感觉的神经基础可以促进新型焦虑症治疗方法的发展。在啮齿动物中，进食状态双向调节类似焦虑的行为，但胃肠道状态的感知如何影响焦虑尚不清楚。
我们结合化学遗传学、神经药理学和行为学方法，在雄性和雌性大鼠中测试终止于胃肠道的迷走传入纤维是否调节进食引起的焦虑变化。我们使用基于皂素的损伤和转录组学方法，研究了该肠道-大脑回路对类似焦虑行为的慢性影响。
进食和选择性化学遗传学激活支配肠道的迷走传入纤维均可增加类似焦虑的行为。相反，化学遗传学抑制阻断了进食引起的类似焦虑行为的增加。使用选择性基于皂素的损伤，我们证明雄性大鼠中，支配肠道的迷走传入纤维信号的丧失会慢性降低类似焦虑的行为，但在雌性大鼠中则不然。我们接下来使用顺行跨突触示踪技术从结状神经节确定了一条连接肠道和杏仁中央核的迷走神经回路，该回路连接肠道和杏仁中央核。该肠道-大脑迷走神经回路的损伤在两性中都调节了中央杏仁核的转录组，但仅在雄性中选择性地影响 GABA（γ-氨基丁酸）相关基因网络，提示抑制控制增强。阻断中央杏仁核中的 GABA 能信号传导可使雄性大鼠恢复正常的焦虑水平。
来自胃肠道的迷走感觉信号通过大鼠的杏仁中央核对基础和进食诱导的焦虑调节至关重要。我们的结果表明，迷走神经肠道-大脑信号传导可作为正常化焦虑障碍内脏感觉的靶点。
Zotero 插件
