Alterations in hypoglossal motor neurons due to GAD67 and VGAT deficiency in mice.
Alterations in hypoglossal motor neurons due to GAD67 and VGAT deficiency in mice.
复制标题
小鼠 GAD67 和 VGAT 缺陷导致舌下运动神经元的改变。
DOI：
10.1016/j.expneurol.2016.12.004
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Bellingham MC.
中科院分区：
文献类型：
--
作者：
Fogarty MJ;Kanjhan R;Yanagawa Y;Noakes PG;Bellingham MC.
越来越多的证据表明，甘氨酸能和GABA能的突触传入运动神经元(MN)有助于调节MN的最终数量和轴突肌肉的神经支配模式。利用突变的谷氨酸脱羧酶67(GAD67)和囊泡抑制性氨基酸转运体(VGAT)缺陷小鼠，研究突触前GABA能和/或甘氨酸能释放不足对运动神经元突触后体树突结构的影响，以及兴奋性和抑制性突触传入MNS的发育。我们使用全细胞膜片钳记录来自脑干切片的E18.5舌下神经节突触电流，并用神经生物素™对这些记录细胞进行染色，高分辨率共聚焦成像和三维重建。GAD67和VGAT缺陷小鼠的舌下MN表现出抑制性神经传递减少和兴奋性突触输入增加。这些变化与树枝长度的增加、树枝分枝的复杂性和刺突密度的增加有关。我们的结果表明，突触前释放的抑制性氨基酸类神经递质是舌下MN形态的有效调节者，也是这一关键发育时间点突触输入的关键调节者。
There is an emerging body of evidence that glycinergic and GABAergic synaptic inputs onto motor neurons (MNs) help regulate the final number of MNs and axonal muscle innervation patterns. Using mutant glutamate decarboxylase 67 (GAD67) and vesicular inhibitory amino acid transporter (VGAT) deficient mice, we describe the effect that deficiencies of presynaptic GABAergic and/or glycinergic release have on the post-synaptic somato-dendritic structure of motor neurons, and the development of excitatory and inhibitory synaptic inputs to MNs. We use whole-cell patch clamp recording of synaptic currents in E18.5 hypoglossal MNs from brainstem slices, combined with dye-filling of these recorded cells with Neurobiotin™, high-resolution confocal imaging and 3-dimensional reconstructions. Hypoglossal MNs from GAD67- and VGAT-deficient mice display decreased inhibitory neurotransmission and increased excitatory synaptic inputs. These changes are associated with increased dendritic arbor length, increased complexity of dendritic branching, and increased density of spiny processes. Our results show that presynaptic release of inhibitory amino acid neurotransmitters are potent regulators of hypoglossal MN morphology and key regulators of synaptic inputs during this critical developmental time point.