Accelerated Development of the First-Order Central Auditory Neurons With Spontaneous Activity.

Accelerated Development of the First-Order Central Auditory Neurons With Spontaneous Activity.
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具有自发活动的一级中枢听觉神经元的加速发育

DOI:
10.3389/fnmol.2018.00183
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发表时间:
2018
影响因子:
4.8
通讯作者:
Yin SK
Yin SK
中科院分区:
医学2区
文献类型:
--
作者:
Yin XL;Jie HQ;Liang M;Gong LN;Liu HW;Pan HL;Xing YZ;Shi HB;Li CY;Wang LY;Yin SK

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在感觉系统的发育中,外周细胞和一阶中枢神经元之间复杂的形态连接在感觉活动开始之前通过遗传编程出现。然而,一级中枢神经元如何获得与外周细胞连接的能力仍然难以捉摸。通过对小鼠脑干脑片进行膜片钳记录,我们发现耳蜗核中的一部分神经元在出生时就表现出自发放电(SFS),并且这种神经元的比例在听力前期增加。兴奋性和抑制性突触输入的阻滞剂可以减少但不能消除SFS,这意味着涉及内在起搏通道。此外,我们证明了这些内源性放电(IF)主要由超极化和环核苷酸门控通道(HCN)介导的电流(Ih)驱动,这一点在HCN阻滞剂存在时或在HCN1基因敲除小鼠的神经元中得到证实。有趣的是,HCN1的基因缺失不能被其他起搏器电导完全补偿,并排除了自发活动神经元的比例及其放电率随年龄的上调。令人惊讶的是,与没有SFS的神经元相比,SFS的神经元在兴奋性、棘波和放电模式以及突触向成熟表型的修剪方面都表现出更快的发展。我们的结果表明,一阶中枢神经元的SFs可能与外周输入相互促进它们的连接和放电,潜在地使发育中的大脑和外部环境之间的相关活动和串扰成为可能。
In developing sensory systems, elaborate morphological connectivity between peripheral cells and first-order central neurons emerges via genetic programming before the onset of sensory activities. However, how the first-order central neurons acquire the capacity to interface with peripheral cells remains elusive. By making patch-clamp recordings from mouse brainstem slices, we found that a subset of neurons in the cochlear nuclei, the first central station to receive peripheral acoustic impulses, exhibits spontaneous firings (SFs) as early as at birth, and the fraction of such neurons increases during the prehearing period. SFs are reduced but not eliminated by a cocktail of blockers for excitatory and inhibitory synaptic inputs, implicating the involvement of intrinsic pacemaker channels. Furthermore, we demonstrate that these intrinsic firings (IFs) are largely driven by hyperpolarization- and cyclic nucleotide-gated channel (HCN) mediated currents (Ih), as evidenced by their attenuation in the presence of HCN blockers or in neurons from HCN1 knockout mice. Interestingly, genetic deletion of HCN1 cannot be fully compensated by other pacemaker conductances and precludes age-dependent up regulation in the fraction of spontaneous active neurons and their firing rate. Surprisingly, neurons with SFs show accelerated development in excitability, spike waveform and firing pattern as well as synaptic pruning towards mature phenotypes compared to those without SFs. Our results imply that SFs of the first-order central neurons may reciprocally promote their wiring and firing with peripheral inputs, potentially enabling the correlated activity and crosstalk between the developing brain and external environment.
DOI: 10.1038/nn.2803
发表时间: 2011-06
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