Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
PLoS One. 2012;7(11):e48431. doi: 10.1371/journal.pone.0048431. Epub 2012 Nov 1.
Sensory input is essential for the normal development of sensory centers in the brain, such as the somatosensory, visual, auditory, and olfactory systems. Visual deprivation during a specific developmental stage, called the critical period, results in severe and irreversible functional impairments in the primary visual cortex. Olfactory deprivation in the early postnatal period also causes significant developmental defects in the olfactory bulb, the primary center for olfaction. Olfactory bulb interneurons are continuously generated from neural stem cells in the ventricular-subventricular zone, suggesting that the olfactory system has plasticity even in adulthood. Here, we investigated the effect of transient neonatal olfactory deprivation on the addition of interneurons to the glomerular layer of the adult mouse olfactory bulb. We found that the addition of one subtype of interneurons was persistently inhibited even after reopening the naris. BrdU pulse-chase experiments revealed that the neonatal olfactory deprivation predominantly affected an early phase in the maturation of this neuronal subtype in the olfactory bulb. Subjecting the mice to odor stimulation for 6 weeks after naris reopening resulted in significant recovery from the histological and functional defects caused by the olfactory deprivation. These results suggest that a subtype-specific critical period exists for olfactory bulb neurogenesis, but that this period is less strict and more plastic compared with the critical periods for other systems. This study provides new insights into the mechanisms of postnatal neurogenesis and a biological basis for the therapeutic effect of olfactory training.
感觉输入对于大脑中感觉中心（如躯体感觉、视觉、听觉和嗅觉系统）的正常发育至关重要。在特定的发育阶段（称为关键期）剥夺视觉会导致初级视觉皮层严重且不可逆转的功能损伤。在出生后的早期剥夺嗅觉也会导致嗅球（嗅觉的主要中枢）发生显著的发育缺陷。嗅球中间神经元是由脑室下区的神经干细胞持续产生的，这表明嗅觉系统即使在成年后也具有可塑性。在这里，我们研究了短暂的新生期嗅觉剥夺对成年小鼠嗅球颗粒层中中间神经元增加的影响。我们发现，即使重新开放鼻道，一种中间神经元亚型的增加仍持续受到抑制。BrdU 脉冲追踪实验表明，新生期嗅觉剥夺主要影响嗅球中该神经元亚型成熟的早期阶段。在重新开放鼻道后对小鼠进行 6 周的气味刺激，可显著恢复嗅觉剥夺引起的组织学和功能缺陷。这些结果表明，嗅球神经发生存在特定于亚型的关键期，但与其他系统的关键期相比，这个时期不那么严格，具有更大的可塑性。本研究为出生后神经发生的机制以及嗅觉训练的治疗效果提供了新的见解。
