Horie Sawa, Kiyokage Emi, Hayashi Shuichi, Inoue Kanako, Sohn Jaerin, Hioki Hiroyuki, Furuta Takahiro, Toida Kazunori
Department of Anatomy, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare, Kurashiki, Okayama, Japan.
J Comp Neurol. 2021 Jun;529(9):2189-2208. doi: 10.1002/cne.25085. Epub 2020 Dec 27.
Olfactory input is processed in the glomerulus of the main olfactory bulb (OB) and relayed to higher centers in the brain by projection neurons. Conversely, centrifugal inputs from other brain regions project to the OB. We have previously analyzed centrifugal inputs into the OB from several brain regions using single-neuron labeling. In this study, we analyzed the centrifugal noradrenergic (NA) fibers derived from the locus coeruleus (LC), because their projection pathways and synaptic connections in the OB have not been clarified in detail. We analyzed the NA centrifugal projections by single-neuron labeling and immunoelectron microscopy. Individual NA neurons labeled by viral infection were three-dimensionally traced using Neurolucida software to visualize the projection pathway from the LC to the OB. Also, centrifugal NA fibers were visualized using an antibody for noradrenaline transporter (NET). NET immunoreactive (-ir) fibers contained many varicosities and synaptic vesicles. Furthermore, electron tomography demonstrated that NET-ir fibers formed asymmetrical synapses of varied morphology. Although these synapses were present at varicosities, the density of synapses was relatively low throughout the OB. The maximal density of synapses was found in the external plexiform layer; about 17% of all observed varicosities contained synapses. These results strongly suggest that NA-containing fibers in the OB release NA from both varicosities and synapses to influence the activities of OB neurons. The present study provides a morphological basis for olfactory modulation by centrifugal NA fibers derived from the LC.
嗅觉输入在主嗅球（OB）的肾小球中进行处理，并通过投射神经元传递到大脑的更高中枢。相反，来自其他脑区的离心输入投射到OB。我们之前使用单神经元标记分析了来自几个脑区的离心输入到OB的情况。在本研究中，我们分析了源自蓝斑（LC）的离心去甲肾上腺素能（NA）纤维，因为它们在OB中的投射途径和突触连接尚未详细阐明。我们通过单神经元标记和免疫电子显微镜分析了NA离心投射。使用Neurolucida软件对通过病毒感染标记的单个NA神经元进行三维追踪，以可视化从LC到OB的投射途径。此外，使用去甲肾上腺素转运体（NET）抗体可视化离心NA纤维。NET免疫反应性（-ir）纤维包含许多曲张体和突触小泡。此外，电子断层扫描显示NET-ir纤维形成了形态各异的不对称突触。虽然这些突触存在于曲张体处，但整个OB中的突触密度相对较低。在外部丛状层中发现突触的最大密度；所有观察到的曲张体中约17%含有突触。这些结果有力地表明，OB中含NA的纤维从曲张体和突触中释放NA，以影响OB神经元的活动。本研究为源自LC的离心NA纤维对嗅觉的调节提供了形态学基础。
