Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, United States.
Department of Biology, University of San Diego, San Diego, United States.
Elife. 2024 Oct 18;13:RP95402. doi: 10.7554/eLife.95402.
Mapping neurotransmitter identities to neurons is key to understanding information flow in a nervous system. It also provides valuable entry points for studying the development and plasticity of neuronal identity features. In the nervous system, neurotransmitter identities have been largely assigned by expression pattern analysis of neurotransmitter pathway genes that encode neurotransmitter biosynthetic enzymes or transporters. However, many of these assignments have relied on multicopy reporter transgenes that may lack relevant -regulatory information and therefore may not provide an accurate picture of neurotransmitter usage. We analyzed the expression patterns of 16 CRISPR/Cas9-engineered knock-in reporter strains for all main types of neurotransmitters in (glutamate, acetylcholine, GABA, serotonin, dopamine, tyramine, and octopamine) in both the hermaphrodite and the male. Our analysis reveals novel sites of expression of these neurotransmitter systems within both neurons and glia, as well as non-neural cells, most notably in gonadal cells. The resulting expression atlas defines neurons that may be exclusively neuropeptidergic, substantially expands the repertoire of neurons capable of co-transmitting multiple neurotransmitters, and identifies novel sites of monoaminergic neurotransmitter uptake. Furthermore, we also observed unusual co-expression patterns of monoaminergic synthesis pathway genes, suggesting the existence of novel monoaminergic transmitters. Our analysis results in what constitutes the most extensive whole-animal-wide map of neurotransmitter usage to date, paving the way for a better understanding of neuronal communication and neuronal identity specification in .
将神经递质的身份映射到神经元是理解神经系统信息流的关键。它也为研究神经元身份特征的发育和可塑性提供了有价值的切入点。在神经系统中，神经递质的身份主要是通过编码神经递质生物合成酶或转运体的神经递质途径基因的表达模式分析来分配的。然而，许多这些分配依赖于多拷贝的报告基因转染体，这些转染体可能缺乏相关的调节信息，因此可能无法提供神经递质使用的准确图像。我们分析了 16 种 CRISPR/Cas9 工程敲入报告菌株在雌雄同体和雄性中的所有主要类型神经递质（谷氨酸、乙酰胆碱、GABA、血清素、多巴胺、酪胺和章鱼胺）的表达模式。我们的分析揭示了这些神经递质系统在神经元和神经胶质细胞以及非神经细胞中的新表达部位，尤其是在性腺细胞中。由此产生的表达图谱定义了可能仅为神经肽的神经元，大大扩展了能够共传递多种神经递质的神经元的范围，并确定了单胺类神经递质摄取的新部位。此外，我们还观察到单胺合成途径基因的异常共表达模式，表明存在新的单胺类神经递质。我们的分析结果构成了迄今为止最广泛的全动物范围神经递质使用图谱，为更好地理解神经元通信和神经元身份指定铺平了道路。
