Abstract:
Sensory experience affects not only the corresponding primary sensory cortex, but also synaptic and neural circuit functions in other brain regions in a cross-modal manner. However, it remains unclear whether oligodendrocyte (OL) generation and myelination can also undergo cross-modal modulation. Here, we report that while early life short-term whisker deprivation from birth significantly reduces in the number of mature of OLs and the degree of myelination in the primary somatosensory cortex(S1) at postnatal day 14 (P14), it also simultaneously affects the primary visual cortex (V1), but not the medial prefrontal cortex (mPFC) with a similar reduction. Interestingly, when mice were subjected to long-term early whisker deprivation from birth (P0) to P35, they exhibited dramatically impaired myelination and a deduced number of differentiated OLs in regions including the S1, V1, and mPFC, as detected at P60. Meanwhile, the process complexity of OL precursor cells (OPCs) was also rduced, as detected in the mPFC. However, when whisker deprivation occurred during the mid-late postnatal period (P35 to P50), myelination was unaffected in both V1 and mPFC brain regions at P60. In addition to impaired OL and myelin development in the mPFC, long-term early whisker-deprived mice also showed deficits in social novelty, accompanied by abnormal activation of c-Fos in the mPFC. Thus, our results reveal a novel form of cross-modal modulation of myelination by sensory experience that can lead to abnormalities in social behavioral, suggesting a possible similar mechanism underlying brain pathological conditions that suffer from both sensory and social behavioral deficits, such as autism spectrum disorders.
摘要:
感觉体验不仅影响相应的初级感觉皮层,但突触和神经回路也以交叉模式的方式在其他大脑区域发挥作用。然而,目前尚不清楚少突胶质细胞(OL)的产生和髓鞘形成是否也可以进行交叉模式调制.这里,我们报告说,虽然生命早期的短期晶须剥夺从出生后第14天(P14)显著减少成熟的OLs的数量和初级体感皮层(S1)的髓鞘形成程度,它也同时影响初级视觉皮层(V1),但内侧前额叶皮质(mPFC)没有类似的减少。有趣的是,当小鼠从出生(P0)到P35长期早期晶须剥夺时,它们表现出明显的髓鞘形成受损,并在包括S1,V1和mPFC在内的区域中推导出分化的OLs数量,在P60检测到。同时,还降低了OL前体细胞(OPC)的过程复杂性,在mPFC中检测到。然而,当胡须剥夺发生在产后中后期(P35至P50),在P60时,V1和mPFC脑区的髓鞘形成均不受影响。除了mPFC中的OL和髓磷脂发育受损之外,长期的早期胡须剥夺小鼠也表现出社会新颖性的缺陷,伴随着mPFC中c-Fos的异常激活。因此,我们的研究结果揭示了一种新形式的交叉模态调制髓鞘形成的感官经验,可以导致异常的社会行为,提示大脑病理状况可能存在类似的机制,这些疾病同时存在感官和社会行为缺陷,比如自闭症谱系障碍。