Sánchez-Guardado Luis, Razavi Peyman, Wang Bo, Callejas-Marín Antuca, Lois Carlos
Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
Department of Cell Biology, School of Science, University of Extremadura, Badajoz, Spain.
Elife. 2024 Dec 13;13:RP90296. doi: 10.7554/eLife.90296.
The assembly and maintenance of neural circuits is crucial for proper brain function. Although the assembly of brain circuits has been extensively studied, much less is understood about the mechanisms controlling their maintenance as animals mature. In the olfactory system, the axons of olfactory sensory neurons (OSNs) expressing the same odor receptor converge into discrete synaptic structures of the olfactory bulb (OB) called glomeruli, forming a stereotypic odor map. The OB projection neurons, called mitral and tufted cells (M/Ts), have a single dendrite that branches into a single glomerulus, where they make synapses with OSNs. We used a genetic method to progressively eliminate the vast majority of M/T cells in early postnatal mice, and observed that the assembly of the OB bulb circuits proceeded normally. However, as the animals became adults the apical dendrite of remaining M/Ts grew multiple branches that innervated several glomeruli, and OSNs expressing single odor receptors projected their axons into multiple glomeruli, disrupting the olfactory sensory map. Moreover, ablating the M/Ts in adult animals also resulted in similar structural changes in the projections of remaining M/Ts and axons from OSNs. Interestingly, the ability of these mice to detect odors was relatively preserved despite only having 1-5% of projection neurons transmitting odorant information to the brain, and having highly disrupted circuits in the OB. These results indicate that a reduced number of projection neurons does not affect the normal assembly of the olfactory circuit, but induces structural instability of the olfactory circuitry of adult animals.
神经回路的组装和维持对于大脑的正常功能至关重要。尽管大脑回路的组装已得到广泛研究，但对于动物成熟后控制其维持的机制却了解甚少。在嗅觉系统中，表达相同气味受体的嗅觉感觉神经元（OSN）的轴突汇聚到嗅球（OB）中称为嗅小球的离散突触结构中，形成一种刻板的气味图谱。OB投射神经元，即僧帽细胞和簇状细胞（M/T），具有单个树突，该树突分支进入单个嗅小球，在那里它们与OSN形成突触。我们使用一种遗传方法逐步消除出生后早期小鼠中的绝大多数M/T细胞，并观察到OB回路的组装正常进行。然而，随着动物成年，剩余M/T细胞的顶端树突长出多个分支，支配多个嗅小球，并且表达单一气味受体的OSN将其轴突投射到多个嗅小球中，从而破坏了嗅觉感觉图谱。此外，在成年动物中消融M/T细胞也导致剩余M/T细胞和OSN轴突投射中出现类似的结构变化。有趣的是，尽管这些小鼠中只有1-5%的投射神经元将气味信息传递到大脑，并且OB中的回路高度紊乱，但它们检测气味的能力相对保留。这些结果表明，投射神经元数量的减少不会影响嗅觉回路的正常组装，但会诱导成年动物嗅觉回路的结构不稳定。
