Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
PLoS One. 2013 Jul 29;8(7):e69862. doi: 10.1371/journal.pone.0069862. Print 2013.
Activity plays critical roles in development and maintenance of the olfactory system, which undergoes considerable neurogenesis throughout life. In the mouse olfactory epithelium, each olfactory sensory neuron (OSN) stably expresses a single odorant receptor (OR) type out of a repertoire of ∼1200 and the OSNs with the same OR identity are distributed within one of the few broadly-defined zones. However, it remains elusive whether and how activity modulates such OR expression patterns. Here we addressed this question by investigating OR gene expression via in situ hybridization when sensory experience or neuronal excitability is manipulated. We first examined the expression patterns of fifteen OR genes in mice which underwent neonatal, unilateral naris closure. After four-week occlusion, the cell density in the closed (sensory-deprived) side was significantly lower (for four ORs), similar (for three ORs), or significantly higher (for eight ORs) as compared to that in the open (over-stimulated) side, suggesting that sensory inputs have differential effects on OSNs expressing different OR genes. We next examined the expression patterns of seven OR genes in transgenic mice in which mature OSNs had reduced neuronal excitability. Neuronal silencing led to a significant reduction in the cell density for most OR genes tested and thinner olfactory epithelium with an increased density of apoptotic cells. These results suggest that sensory experience plays important roles in shaping OR gene expression patterns and the neuronal activity is critical for survival of OSNs.
活动在嗅觉系统的发育和维持中起着关键作用，嗅觉系统在整个生命周期中经历大量的神经发生。在小鼠嗅上皮中，每个嗅觉感觉神经元（OSN）稳定表达 1200 种受体类型中的一种气味受体（OR），并且具有相同 OR 身份的 OSN 分布在少数几个广泛定义的区域之一内。然而，活动是否以及如何调节这种 OR 表达模式仍然难以捉摸。在这里，我们通过在感觉经验或神经元兴奋性受到干扰时通过原位杂交来研究 OR 基因的表达，从而解决了这个问题。我们首先研究了经历新生期单侧鼻孔闭合的小鼠中十五个 OR 基因的表达模式。在四周的闭塞后，与开放（过度刺激）侧相比，闭合（感觉剥夺）侧的细胞密度显著降低（对于四个 OR），相似（对于三个 OR）或显著升高（对于八个 OR），这表明感觉输入对表达不同 OR 基因的 OSN 有不同的影响。接下来，我们研究了在成熟 OSN 兴奋性降低的转基因小鼠中七个 OR 基因的表达模式。神经元沉默导致大多数测试的 OR 基因的细胞密度显著降低，并且嗅觉上皮变薄，凋亡细胞密度增加。这些结果表明，感觉经验在塑造 OR 基因表达模式方面起着重要作用，神经元活动对于 OSN 的存活至关重要。
