Horowitz L F, Montmayeur J P, Echelard Y, Buck L B
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3194-9. doi: 10.1073/pnas.96.6.3194.
Mammalian nervous system function involves billions of neurons which are interconnected in a multitude of neural circuits. Here we describe a genetic approach to chart neural circuits. By using an olfactory-specific promoter, we selectively expressed barley lectin in sensory neurons in the olfactory epithelium and vomeronasal organ of transgenic mice. The lectin was transported through the axons of those neurons to the olfactory bulb, transferred to the bulb neurons with which they synapse, and transported through the axons of bulb neurons to the olfactory cortex. The lectin also was retrogradely transported from the bulb to neuromodulatory brain areas. No evidence could be obtained for adverse effects of the lectin on odorant receptor gene expression, sensory axon targeting in the bulb, or the generation or transmission of signals by olfactory sensory neurons. Transneuronal transfer was detected prenatally in the odor-sensing pathway, but only postnatally in the pheromone-sensing pathway, suggesting that odors, but not pheromones, may be sensed in utero. Our studies demonstrate that a plant lectin can serve as a transneuronal tracer when its expression is genetically targeted to a subset of neurons. This technology can potentially be applied to a variety of vertebrate and invertebrate neural systems and may be particularly valuable for mapping connections formed by small subsets of neurons and for studying the development of connectivity as it occurs in utero.
哺乳动物的神经系统功能涉及数十亿个神经元，这些神经元在众多神经回路中相互连接。在这里，我们描述了一种绘制神经回路的遗传学方法。通过使用嗅觉特异性启动子，我们在转基因小鼠的嗅觉上皮和犁鼻器的感觉神经元中选择性地表达大麦凝集素。凝集素通过这些神经元的轴突运输到嗅球，转移到与它们形成突触的嗅球神经元，并通过嗅球神经元的轴突运输到嗅觉皮层。凝集素也从嗅球逆向运输到神经调节脑区。没有证据表明凝集素对气味受体基因表达、嗅球中感觉轴突靶向或嗅觉感觉神经元信号的产生或传递有不良影响。在气味感知途径中，产前检测到跨神经元转移，但在信息素感知途径中仅在产后检测到，这表明气味而非信息素可能在子宫内被感知。我们的研究表明，当植物凝集素的表达通过基因靶向作用于神经元亚群时，它可以作为一种跨神经元示踪剂。这项技术有可能应用于各种脊椎动物和无脊椎动物的神经系统，对于绘制由小部分神经元形成的连接以及研究子宫内发生的连接发育可能特别有价值。
