Li Yan-Hai, Han Lei, Wu Kenneth Lap Kei, Chan Ying-Shing
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Research Center of Rehabilitation Science and Technology, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, Hong Kong, PR China.
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, Hong Kong, PR China.
Neuropharmacology. 2017 Sep 1;123:242-248. doi: 10.1016/j.neuropharm.2017.05.005. Epub 2017 May 5.
The medial vestibular nucleus (MVN) is a major output station for neurons that project to the vestibulo-spinal pathway. MVN neurons show capacity for long-term depression (LTD) during the juvenile period. We investigated LTD of MVN neurons using whole-cell patch-clamp recordings. High frequency stimulation (HFS) robustly induced LTD in 90% of type B neurons in the MVN, while only 10% of type A neurons were responsive, indicating that type B neurons are the major contributors to LTD in the MVN. The neuromodulator serotonin (5-HT) is known to modulate LTD in neural circuits of the cerebral cortex and the hippocampus. We therefore aim to determine the action of 5-HT on the LTD of type B MVN neurons and elucidate the relevant 5-HT receptor subtypes responsible for its action. Using specific agonists and antagonists of 5-HT receptors, we found that selective activation of 5-HT receptor in type B neurons in the MVN of juvenile (P13-16) rats completely abolished NMDA-receptor-mediated LTD in a protein kinase A (PKA)-dependent manner. Our finding that 5-HT restricts plasticity of type B MVN neurons via 5-HT receptors offers a mechanism whereby vestibular tuning contributes to the maturation of the vestibulo-spinal circuit and highlights the role of 5-HT in postural control.
内侧前庭核（MVN）是投射到前庭脊髓通路的神经元的主要输出站。MVN神经元在幼年时期表现出长时程抑制（LTD）的能力。我们使用全细胞膜片钳记录来研究MVN神经元的LTD。高频刺激（HFS）在MVN中90%的B型神经元中强烈诱导LTD，而只有10%的A型神经元有反应，这表明B型神经元是MVN中LTD的主要贡献者。已知神经调质5-羟色胺（5-HT）可调节大脑皮层和海马体神经回路中的LTD。因此，我们旨在确定5-HT对B型MVN神经元LTD的作用，并阐明负责其作用的相关5-HT受体亚型。使用5-HT受体的特异性激动剂和拮抗剂，我们发现幼年（P13 - 16）大鼠MVN中B型神经元中5-HT受体的选择性激活以蛋白激酶A（PKA）依赖的方式完全消除了NMDA受体介导的LTD。我们的发现表明5-HT通过5-HT受体限制B型MVN神经元的可塑性，这提供了一种机制，通过该机制前庭调谐有助于前庭脊髓回路的成熟，并突出了5-HT在姿势控制中的作用。
