Sympathetic circuits including pre-sympathetic neurons in the ventrolateral medulla (VLM) and in the paraventricular nucleus (PVN) of the hypothalamus play an important role in the regulation of hepatic glucose metabolism. Despite the importance of central regulatory pathways, specific information regarding the circuits of liver-related neurons is limited. Here, we tested the hypothesis that PVN neurons are directly connected to spinally-projecting liver-related neurons in the VLM of mice. Pseudorabies virus (PRV) was used to identify liver-related neurons and time-dependent analyses revealed the location and distribution of neurons in the PVN and ventral brainstem. Four days following PRV injection, most liver-related neurons were found in the VLM and consist of both catecholaminergic (CA) and non-CA neurons. Furthermore, in addition to PRV inoculation, a monosynaptic viral tracer was used to identify VLM-projecting PVN neurons to specifically dissect PVN-VLM connections within the liver pathway. Five days following PRV inoculation, our anatomical findings revealed that a small population of liver-related PVN neurons projected to the VLM. In addition, photo-stimulation of axonal projections from SIM1-expressing PVN neurons resulted in evoked excitatory postsynaptic currents in a subset of spinally projecting liver-related neurons in the VLM. In summary, our data demonstrate the existence of monosynaptic, glutamatergic connections between PVN neurons and pre-sympathetic liver-related neurons in the VLM. These new findings regarding the central circuits involved in the sympathetic regulation of the liver provide further information necessary for developing new strategies to improve glucose homeostasis via modulation of the autonomic nerves.

中文翻译：

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下丘脑室旁核中的神经元亚群直接投射到腹外侧延髓中与肝脏相关的前运动神经元


交感神经回路，包括腹外侧延髓 （VLM） 和下丘脑室旁核 （PVN） 中的交感神经前神经元，在肝脏葡萄糖代谢的调节中起重要作用。尽管中枢调节通路很重要，但有关肝脏相关神经元回路的具体信息有限。在这里，我们检验了 PVN 神经元与小鼠 VLM 中脊髓投射的肝脏相关神经元直接相关的假设。伪狂犬病病毒 （PRV） 用于识别肝脏相关神经元，时间依赖性分析揭示了神经元在 PVN 和腹侧脑干中的位置和分布。注射 PRV 后 4 天，在 VLM 中发现了大多数肝脏相关神经元，由儿茶酚胺能 （CA） 和非 CA 神经元组成。此外，除了 PRV 接种外，还使用单突触病毒示踪剂来识别投射 VLM 的 PVN 神经元，以特异性解剖肝脏通路内的 PVN-VLM 连接。PRV 接种后 5 天，我们的解剖学结果显示，一小群肝脏相关 PVN 神经元投射到 VLM。此外，对表达 SIM1 的 PVN 神经元的轴突投射进行光刺激，导致 VLM 中脊髓投射的肝脏相关神经元子集中诱发兴奋性突触后电流。总之，我们的数据表明 VLM 中的 PVN 神经元和前交感神经肝脏相关神经元之间存在单突触、谷氨酸能连接。这些关于肝脏交感神经调节中枢回路的新发现为开发通过调节自主神经来改善葡萄糖稳态的新策略提供了必要的进一步信息。