Role of CX3CR1 Signaling on the Maturation of GABAergic Transmission and Neuronal Network Activity in the Neonate Hippocampus
Role of CX3CR1 Signaling on the Maturation of GABAergic Transmission and Neuronal Network Activity in the Neonate Hippocampus
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DOI：
10.1016/j.neuroscience.2019.03.006
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发表时间：
2019-05-15
期刊：
影响因子：
3.3
通讯作者：
Avignone, Elena
中科院分区：
文献类型：
--
作者：
Bertot, Charlotte;Groc, Laurent;Avignone, Elena
在发育中的大脑中，小胶质细胞在塑造神经元回路中发挥着重要作用。这些免疫细胞通过 fractalkine (CX3CL1) 与神经元进行通信，fractalkine (CX3CL1) 是一种作用于小胶质细胞 CX3CR1 受体的神经元细胞因子。在各种功能中，该信号通路与谷氨酸能突触的出生后成熟有关。尽管当 GABA 受体介导的突触传递和同步振荡事件发生时，新生儿海马中存在小胶质细胞，但小胶质细胞是否调节这些活动的建立仍不清楚。使用CX3CR1缺陷小鼠和电生理学手段，我们在CA3锥体神经元中研究了fratalkine信号传导在GABA（A）受体介导的突触电流和巨去极化电位（GDP）成熟中的作用，GDP是一种对塑造突触连接很重要的网络活动。在CX3CR1缺陷小鼠中，GABA能电流略有改变，而这些电流的发育变化与野生型动物相当。尽管 GABA 能传递发生这些微小变化，但与野生型相比，CX3CR1 缺陷小鼠的 GDP 频率显着降低，且 GDP 形状和结束周期没有变化。总的来说，在新生儿海马体中，fractalkine 信号通路调节 GDP 活性，并少量参与 GABA 能突触的成熟，这表明小胶质细胞对 GABA 能、谷氨酸能和网络功能的成熟具有明显的影响。 (C) 2019 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
In the developing brain, microglial cells play an important role in shaping neuronal circuits. These immune cells communicate with neurons through fractalkine (CX3CL1), a neuronal cytokine that acts on microglial CX3CR1 receptor. Among various functions, this signaling pathway has been implicated in the postnatal maturation of glutamatergic synapses. Although microglial cells are present in the neonate hippocampus when GABA receptor-mediated synaptic transmission and synchronized oscillatory events take place, it remains unknown whether microglial cells tune the establishment of these activities. Using CX3CR1-deficient mice and electrophysiological means, we investigated in CA3 pyramidal neurons the role of the fractalkine signaling in the maturation of GABA(A) receptor-mediated synaptic currents and giant depolarizing potentials (GDPs), a network activity important for shaping synaptic connections. In CX3CR1-deficient mice, GABAergic currents were slightly altered, whereas the developmental changes of these currents were comparable with wild-type animals. Despite these minor changes in GABAergic transmission, the GDP frequency was strikingly reduced in CX3CR1-deficient mice compared to wild-type, with no change in the GDP shape and ending period. Collectively, it emerges that, in the neonate hippocampus, the fractalkine signaling pathway tunes GDP activities and is marginally involved in the maturation of GABAergic synapses, suggesting that microglial cells have distinct impact on maturing GABAergic, glutamatergic, and network functions. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.