Department of Neurosciences, University of California, San Diego, La Jolla, California 92093.
Department of Neurosciences, University of California, San Diego, La Jolla, California 92093
eNeuro. 2019 Aug 20;6(4). doi: 10.1523/ENEURO.0161-19.2019. Print 2019 Jul/Aug.
Vesicular glutamate transporters (VGLUTs) mediate the synaptic uptake of glutamate from the cytosol into synaptic vesicles and are considered unambiguous neurochemical markers of glutamate neurons. However, many neurons not classically thought of as glutamatergic also express a VGLUT and co-release glutamate. Using a genetic fate-mapping strategy we found that most cholinergic neurons in the mouse mesopontine tegmentum express VGLUT2 at some point during development, including the pedunculopontine tegmental nucleus (PPTg), laterodorsal tegmental nucleus, and parabigeminal nucleus (PBG), but not the oculomotor nucleus. In contrast, very few of these cholinergic neurons displayed evidence of vesicular GABA transporter expression. Using multiplex fluorescent hybridization, we determined that only PBG cholinergic neurons are also predominantly positive for VGLUT2 mRNA in the adult, with only small numbers of PPTg cholinergic neurons overlapping with VGLUT2 mRNA. Using Cre-dependent viral vectors we confirm these hybridization data, and demonstrate projection patterns of cholinergic and glutamatergic populations. These results demonstrate that most mesopontine cholinergic neurons may transiently express VGLUT2, but that a large majority of PBG neurons retain VGLUT2 expression throughout adulthood, and support a growing body of literature indicating that distinct cholinergic populations have differing potential for GABA or glutamate co-release.
囊泡谷氨酸转运体（VGLUTs）介导细胞溶质中谷氨酸向突触小泡的突触摄取，被认为是谷氨酸能神经元的明确神经化学标志物。然而，许多通常不被认为是谷氨酸能的神经元也表达 VGLUT 并共同释放谷氨酸。使用遗传命运映射策略，我们发现，在发育过程中的某个阶段，大多数小鼠中脑桥被盖腹侧区的胆碱能神经元表达 VGLUT2，包括脚桥核被盖部（PPTg）、外侧被盖核和成对臂旁核（PBG），但动眼神经核除外。相比之下，这些胆碱能神经元中很少有显示出囊泡 GABA 转运体表达的证据。使用多重荧光杂交，我们确定只有 PBG 胆碱能神经元在成年时也主要为 VGLUT2 mRNA 阳性，只有少数 PPTg 胆碱能神经元与 VGLUT2 mRNA 重叠。使用 Cre 依赖性病毒载体，我们证实了这些杂交数据，并展示了胆碱能和谷氨酸能群体的投射模式。这些结果表明，大多数中脑桥胆碱能神经元可能短暂表达 VGLUT2，但大多数 PBG 神经元在整个成年期都保留 VGLUT2 表达，并支持越来越多的文献表明，不同的胆碱能群体具有不同的 GABA 或谷氨酸共同释放的潜力。
