Qi Meizhu, Won Julia, Rodriguez Catherine, Storace Douglas A
Department of Biological Science, Florida State University, Tallahassee, FL.
Program in Neuroscience, Florida State University, Tallahassee, FL.
bioRxiv. 2025 Feb 16:2025.02.16.638511. doi: 10.1101/2025.02.16.638511.
The direct pathway from the lateral hypothalamus to the mouse olfactory bulb (OB) includes neurons that express the neuropeptide orexin-A, and others that do not. The OB-projecting neurons that do not express orexin-A are present in an area of the lateral hypothalamus known to contain neurons that express the neuropeptide melanin-concentrating hormone (MCH). We used virally mediated anterograde tract tracing and immunohistochemistry for orexin-A and MCH to demonstrate that the OB is broadly innervated by axon projections from both populations of neurons. Orexin-A and MCH were expressed in each OB layer across its anterior to posterior axis. Both orexin-A and MCH neurons are genetically heterogeneous, with subsets that co-express an isoform of vesicular glutamate transporter (VGLUT). We used high-resolution confocal imaging to test whether the projections from orexin-A and MCH neurons to the OB reflect this glutamatergic heterogeneity. The majority (~57%) of putative orexin-A axon terminals overlapped with VGLUT2, with smaller proportions that co-expressed VGLUT1, or that did not overlap with either VGLUT1 or VGLUT2. In contrast, only ~26% of putative MCH axon terminals overlapped with VGLUT2, with the majority not overlapping with either VGLUT. Therefore, the projections from the lateral hypothalamus to the OB are genetically heterogeneous and include neurons that can release two different neuropeptides. The projections from both populations are themselves genetically heterogeneous with distinct ratios of glutamatergic and non-glutamatergic axon terminals.
从外侧下丘脑到小鼠嗅球（OB）的直接通路包括表达神经肽增食欲素-A的神经元和不表达该神经肽的其他神经元。不表达增食欲素-A的投射至OB的神经元存在于外侧下丘脑的一个区域，已知该区域含有表达神经肽促黑素细胞激素（MCH）的神经元。我们利用病毒介导的顺行束路追踪以及针对增食欲素-A和MCH的免疫组织化学方法，证明OB广泛地接受这两类神经元轴突投射的支配。增食欲素-A和MCH在OB从前到后的各层中均有表达。增食欲素-A和MCH神经元在基因上均具有异质性，其中一些亚群共表达囊泡型谷氨酸转运体（VGLUT）的一种异构体。我们利用高分辨率共聚焦成像技术来检测从增食欲素-A和MCH神经元到OB的投射是否反映了这种谷氨酸能的异质性。大部分（约57%）假定的增食欲素-A轴突终末与VGLUT2重叠，一小部分共表达VGLUT1，或者不与VGLUT1或VGLUT2中的任何一种重叠。相比之下，只有约26%的假定MCH轴突终末与VGLUT2重叠，大多数不与任何一种VGLUT重叠。因此，从外侧下丘脑到OB的投射在基因上具有异质性，并且包括能够释放两种不同神经肽的神经元。这两类神经元的投射本身在基因上也具有异质性，谷氨酸能和非谷氨酸能轴突终末的比例各不相同。
