Synaptic Inputs to the Mouse Dorsal Vagal Complex and Its Resident Preproglucagon Neurons
Synaptic Inputs to the Mouse Dorsal Vagal Complex and Its Resident Preproglucagon Neurons
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DOI：
10.1523/jneurosci.2145-19.2019
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发表时间：
2019-12-04
影响因子：
5.3
通讯作者：
Rinaman, Linda
中科院分区：
文献类型：
--
作者：
Holt, Marie K.;Pomeranz, Lisa E.;Rinaman, Linda
压力反应由广泛的神经回路协调。稳态和心理应激源激活孤束尾核 (cNTS) 中的前胰高血糖素 (PPG) 神经元，产生胰高血糖素样肽-1；已发表的啮齿类动物研究表明，这些神经元在应激反应中发挥着至关重要的作用。虽然 PPG 神经元的轴突目标已经明确，但它们的传入输入尚不清楚。在这里，我们使用霍乱毒素 b 亚基逆行追踪来表明雄性和雌性小鼠的 cNTS 接收的轴突输入与大鼠中报道的相似。使用 Cre 条件伪狂犬病和狂犬病病毒揭示了 cNTS PPG 神经元特异的单突触和多突触输入。 PPG 单突触输入最重要的来源包括下丘脑的外侧 (LH) 和室旁 (PVN) 核、下丘脑旁核、中央杏仁核的外侧部分和巴林顿核 (Bar)。此外，PPG 神经元接收来自结状神经节的单突触迷走神经感觉输入和来自背角的脊髓感觉输入。 cNTS PPG 神经元的多突触输入来源包括海马结构、室旁丘脑和前额皮质。最后，在约束应激后，PVN、LH 和 Bar 内的 cNTS 投射神经元在小鼠中表达激活标记 cFOS，将它们识别为神经源性应激诱导 PPG 神经元募集的潜在来源。总之，小鼠的 cNTS PPG 神经元从涉及协调行为和生理应激反应的大脑区域以及迷走神经和脊髓感觉神经元接收广泛的单突触和多突触输入。因此，PPG 神经元处于最佳位置，可以整合稳态和心因性应激信号。
Stress responses are coordinated by widespread neural circuits. Homeostatic and psychogenic stressors activate preproglucagon (PPG) neurons in the caudal nucleus of the solitary tract (cNTS) that produce glucagon-like peptide-1; published work in rodents indicates that these neurons play a crucial role in stress responses. While the axonal targets of PPG neurons are well established, their afferent inputs are unknown. Here we use retrograde tracing with cholera toxin subunit b to show that the cNTS in male and female mice receives axonal inputs similar to those reported in rats. Monosynaptic and polysynaptic inputs specific to cNTS PPG neurons were revealed using Cre-conditional pseudorabies and rabies viruses. The most prominent sources of PPG monosynaptic input include the lateral (LH) and paraventricular (PVN) nuclei of the hypothalamus, parasubthalamic nucleus, lateral division of the central amygdala, and Barrington's nucleus (Bar). Additionally, PPG neurons receive monosynaptic vagal sensory input from the nodose ganglia and spinal sensory input from the dorsal horn. Sources of polysynaptic input to cNTS PPG neurons include the hippocampal formation, paraventricular thalamus, and prefrontal cortex. Finally, cNTS-projecting neurons within PVN, LH, and Bar express the activation marker cFOS in mice after restraint stress, identifying them as potential sources of neurogenic stress-induced recruitment of PPG neurons. In summary, cNTS PPG neurons in mice receive widespread monosynaptic and polysynaptic input from brain regions implicated in coordinating behavioral and physiological stress responses, as well as from vagal and spinal sensory neurons. Thus, PPG neurons are optimally posit ioned to integrate signals of homeostatic and psychogenic stress.