Department of Anatomy, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Department of Medical Technology, Kawasaki University of Medical Welfare, Kurashiki, Okayama, Japan.
J Comp Neurol. 2024 Oct;532(10):e25671. doi: 10.1002/cne.25671.
Odor information is modulated by centrifugal inputs from other brain regions to the olfactory bulb (OB). Neurons containing monoamines, such as serotonin, acetylcholine, and noradrenaline, are well known as centrifugal inputs; however, the role of histamine, which is also present in the OB, is not well understood. In this study, we examined the histaminergic neurons projecting from the hypothalamus to the OB. We used an antibody against histidine decarboxylase (HDC), a synthesizing enzyme of histamine, to identify histaminergic neurons and assess their localization within the OB and the ultrastructure of their fibers and synapses using multiple immunostaining laser microscopy, ultra-high voltage electron microscopy (EM), and EM to confirm their relationships with other neurons. To further identify the origin nucleus of the histaminergic neurons projecting to the OB, we injected the retrograde tracer FluoroGold and analyzed the pathway to the OB anterogradely. HDC-immunoreactive (-ir) fibers were abundant in the olfactory nerve (ON) layer compared to other monoamines. HDC-ir neurons received asymmetrical synapses from ONs and formed synapses containing pleomorphic vesicles with variable postsynaptic densities to non-ON elements, thus forming serial synapses. We also confirmed that histaminergic neurons project from the rostral ventral tuberomammillary nucleus to the granule cell layer of the OB and, for the first time, successfully visualized their axons from the hypothalamus to the OB. These findings indicate that histamine may regulate odor discrimination in the OB, suggesting a regulatory relationship between hypothalamic function and olfaction. We thus elucidate morphological mechanisms with tuberomammillary nucleus-derived histaminergic neurons involved in olfactory information.
气味信息受到来自其他脑区向嗅球（OB）的离心输入的调制。含有单胺的神经元，如血清素、乙酰胆碱和去甲肾上腺素，是众所周知的离心输入；然而，组胺的作用，尽管它也存在于 OB 中，但其作用尚未得到很好的理解。在这项研究中，我们检查了从下丘脑投射到 OB 的组胺能神经元。我们使用抗组氨酸脱羧酶（HDC）的抗体，组氨酸的合成酶，来识别组胺能神经元，并使用多重免疫荧光激光显微镜、超高电压电子显微镜（EM）和 EM 评估它们在 OB 中的定位及其纤维和突触的超微结构，以确认它们与其他神经元的关系。为了进一步确定投射到 OB 的组胺能神经元的起源核，我们注射了逆行示踪剂 FluoroGold，并分析了它们投射到 OB 的前向通路。与其他单胺相比，HDC-免疫反应性（ir）纤维在嗅神经（ON）层中更为丰富。HDC-ir 神经元从 ON 接收不对称突触，并形成含有形态多样的小泡的突触，其突触后密度可变，与非 ON 元件形成串联突触。我们还证实，组胺能神经元从腹侧前结节乳头体核投射到 OB 的颗粒细胞层，并且首次成功地从下丘脑可视化到 OB 的它们的轴突。这些发现表明组胺可能在 OB 中调节气味辨别，提示下丘脑功能和嗅觉之间存在调节关系。因此，我们阐明了涉及嗅觉信息的结节乳头体源性组胺能神经元的形态学机制。
