Collagen XIX is required for pheromone recognition and glutamatergic synapse formation in mouse accessory olfactory bulb.

Collagen XIX is required for pheromone recognition and glutamatergic synapse formation in mouse accessory olfactory bulb.
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DOI:
10.3389/fncel.2023.1157577
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发表时间:
2023
影响因子:
5.3
通讯作者:
--
中科院分区:
医学2区
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--
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在哺乳动物中,副嗅球(AOB)接收来自犁鼻感觉神经元(VSN)的输入,所述犁鼻感觉神经元检测信息素,动物释放的化学线索,以调节同一物种的其他动物的生理或行为。细胞结构上,AOB内的细胞被分离成肾小球层(GL)、二尖瓣细胞层(MCL)和颗粒细胞层(GCL)。虽然这些层的细胞和电路已经被很好地研究,但小鼠AOB中这种电路组装的分子机制仍然不清楚。为了确定AOB中的突触发生机制,我们的注意力被吸引到胶原蛋白XIX,这是一种由哺乳动物端脑神经元产生的非纤维状胶原蛋白,以前已被证明可以调节突触的组装。在这里,我们使用了一个靶向的小鼠突变体,缺乏胶原蛋白XIX的整体和条件等位基因允许细胞特异性删除这种胶原蛋白,以测试是否胶原蛋白XIX的损失导致受损的突触在小鼠AOB。这些分析不仅揭示了这些胶原蛋白XIX缺陷突变体中兴奋性突触分布的缺陷,而且还表明这些突变小鼠表现出对信息素的行为反应改变。虽然这种胶原蛋白已被证明在端脑发挥突触发生的作用,这些作用是在体周抑制性突触,这里的结果是第一次证明这种非传统的胶原蛋白在神经元突触形成的功能。
In mammals, the accessory olfactory bulb (AOB) receives input from vomeronasal sensory neurons (VSN) which detect pheromones, chemical cues released by animals to regulate the physiology or behaviors of other animals of the same species. Cytoarchitecturally, cells within the AOB are segregated into a glomerular layer (GL), mitral cell layer (MCL), and granule cell layer (GCL). While the cells and circuitry of these layers has been well studied, the molecular mechanism underlying the assembly of such circuitry in the mouse AOB remains unclear. With the goal of identifying synaptogenic mechanisms in AOB, our attention was drawn to Collagen XIX, a non-fibrillar collagen generated by neurons in the mammalian telencephalon that has previously been shown to regulate the assembly of synapses. Here, we used both a targeted mouse mutant that lacks Collagen XIX globally and a conditional allele allowing for cell-specific deletion of this collagen to test if the loss of Collagen XIX causes impaired synaptogenesis in the mouse AOB. These analyses not only revealed defects in excitatory synapse distribution in these Collagen XIX-deficient mutants, but also showed that these mutant mice exhibit altered behavioral responses to pheromones. Although this collagen has been demonstrated to play synaptogenic roles in the telencephalon, those roles are at perisomatic inhibitory synapses, results here are the first to demonstrate the function of this unconventional collagen in glutamatergic synapse formation.
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