A specific GABAergic synapse onto oligodendrocyte precursors does not regulate cortical oligodendrogenesis
A specific GABAergic synapse onto oligodendrocyte precursors does not regulate cortical oligodendrogenesis
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DOI：
10.1002/glia.23197
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发表时间：
2017-11-01
期刊：
影响因子：
6.2
通讯作者：
Angulo, Maria Cecilia
中科院分区：
文献类型：
--
作者：
Balia, Maddalena;Benamer, Najate;Angulo, Maria Cecilia
在大脑中，神经元在少突胶质前体细胞（OPCs）上建立真正的突触，但这些神经元-胶质突触的功能仍然没有得到解决。一个主要的假设表明，这些突触调节OPC的增殖和分化。然而，突触活动和OPC细胞动力学之间的因果关系仍然缺失。在发育中的躯体感觉皮层中，OPCs接受来自GABA能中间神经元的主要类型的突触，该突触由含有GABA（A）受体的突触后2介导。在这里，我们遗传沉默这些受体在OPCs的关键时期的皮质少突分化。我们发现2-介导的突触失活不影响OPC增殖和分化或OPC的突触前中间神经元髓鞘化倾向。然而，这种失活导致OPC池的进行性和特异性耗尽，缺乏2-介导的突触活性，而不影响少突胶质细胞的产生。我们的研究结果表明，在皮质发育过程中，2-介导的interneuron-OPC突触不发挥作用，少突分化，并建议这些突触微调OPC自我维持能力。他们还打开了一个有趣的可能性，一个特定的突触信号到OPC发挥特定的作用，根据释放的神经递质，突触前神经元的身份或突触后受体参与OPC功能。
In the brain, neurons establish bona fide synapses onto oligodendrocyte precursor cells (OPCs), but the function of these neuron-glia synapses remains unresolved. A leading hypothesis suggests that these synapses regulate OPC proliferation and differentiation. However, a causal link between synaptic activity and OPC cellular dynamics is still missing. In the developing somatosensory cortex, OPCs receive a major type of synapse from GABAergic interneurons that is mediated by postsynaptic 2-containing GABA(A) receptors. Here we genetically silenced these receptors in OPCs during the critical period of cortical oligodendrogenesis. We found that the inactivation of 2-mediated synapses does not impact OPC proliferation and differentiation or the propensity of OPCs to myelinate their presynaptic interneurons. However, this inactivation causes a progressive and specific depletion of the OPC pool that lacks 2-mediated synaptic activity without affecting the oligodendrocyte production. Our results show that, during cortical development, the 2-mediated interneuron-to-OPC synapses do not play a role in oligodendrogenesis and suggest that these synapses finely tune OPC self-maintenance capacity. They also open the interesting possibility that a particular synaptic signaling onto OPCs plays a specific role in OPC function according to the neurotransmitter released, the identity of presynaptic neurons or the postsynaptic receptors involved.