Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306.
Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306
J Neurosci. 2024 Jul 31;44(31):e2063232024. doi: 10.1523/JNEUROSCI.2063-23.2024.
Neurons in the caudal nucleus of the solitary tract (cNTS) and intermediate reticular nucleus (IRt) that express the glucagon gene () give rise to glucagon-like peptide 1 (GLP1)-immunopositive axons in the spinal cord and many subcortical brain regions. Central GLP1 receptor signaling contributes to motivated behavior and stress responses in rats and mice, in which hindbrain GLP1 neurons are activated to express c-Fos in a metabolic state-dependent manner. The present study examined whether GLP1 inputs to distinct brain regions arise from distinct subsets of -expressing neurons, and mapped the distribution of axon collaterals arising from projection-defined GLP1 neural populations. Using our Gcg-Cre knock-in rat model, Cre-dependent adeno-associated virus (AAV) tracing was conducted in adult male and female rats to compare axonal projections of IRt versus cNTS GLP1 neurons. Overlapping projections were observed in all brain regions that receive GLP1 input, with the caveat that cNTS injections produced Cre-dependent labeling of some IRt neurons, and vice versa. In additional experiments, specific diencephalic or limbic forebrain nuclei were microinjected with Cre-dependent retrograde AAVs (AAVrg) that expressed reporters to fully label the axon collaterals of transduced GLP1 neurons. AAVrg injected into each forebrain site labeled -expressing neurons in both the cNTS and IRt. The collective axon collaterals of labeled neurons entered the spinal cord and every brain region previously reported to contain GLP1-positive axons. These results indicate that the axons of GLP1 neural populations that innervate the thalamic paraventricular nucleus, paraventricular nucleus of the hypothalamus, and/or bed nucleus of the stria terminalis collectively innervate all central regions that receive GLP1 axonal input.
孤束核尾侧部（cNTS）和中间网状核（IRt）中的神经元表达胰高血糖素基因（），它们在脊髓和许多皮质下脑区产生胰高血糖素样肽 1（GLP1）免疫阳性轴突。中枢 GLP1 受体信号通路有助于大鼠和小鼠的动机行为和应激反应，其中后脑 GLP1 神经元在代谢状态依赖性方式下被激活以表达 c-Fos。本研究旨在检验 GLP1 传入不同脑区是否来自不同表达的神经元亚群，并绘制源自投射定义的 GLP1 神经元群体的轴突侧支的分布图谱。使用我们的 Gcg-Cre 敲入大鼠模型，在成年雄性和雌性大鼠中进行 Cre 依赖性腺相关病毒（AAV）示踪，以比较 IRt 与 cNTS GLP1 神经元的轴突投射。在所有接受 GLP1 传入的脑区都观察到重叠的投射，需要注意的是，cNTS 注射会导致一些 IRt 神经元产生 Cre 依赖性标记，反之亦然。在额外的实验中，特定的间脑或边缘前脑核被 Cre 依赖性逆行 AAV（AAVrg）注射，该 AAV 表达报告基因以充分标记转导的 GLP1 神经元的轴突侧支。注射到每个前脑部位的 AAVrg 标记了 cNTS 和 IRt 中的表达神经元。标记神经元的集体轴突侧支进入脊髓和以前报道含有 GLP1 阳性轴突的所有脑区。这些结果表明，支配丘脑室旁核、下丘脑室旁核和/或终纹床核的 GLP1 神经元群体的轴突共同支配所有接受 GLP1 轴突传入的中枢区域。
