Sun Mu, Thomas Mark J, Herder Rachel, Bofenkamp M Lisa, Selleck Scott B, O'Connor Michael B
Howard Hughes Medical Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Neurosci. 2007 Jul 18;27(29):7740-50. doi: 10.1523/JNEUROSCI.1604-07.2007.
Recently, several evolutionary conserved signaling pathways that play prominent roles in regulating early neurodevelopment have been found to regulate synaptic remodeling in the adult. To test whether adult neuronal expression of bone morphogenic protein (BMP) signaling components also plays a postnatal role in regulating neuronal plasticity, we modulated BMP signaling in mice both in vivo and in vitro by genetic removal of the BMP inhibitor chordin or by perfusing recombinant BMP signaling pathway components onto acute hippocampal slices. Chordin null mice exhibited a significant increase in presynaptic transmitter release from hippocampal neurons, resulting in enhanced paired-pulse facilitation and long-term potentiation. These mice also showed a decreased acquisition time in a water maze test along with less exploratory activity during Y-maze and open-field tests. Perfusion of BMP ligands onto hippocampal slices replicated the presynaptic phenotype of chordin null slices, but bath application of Noggin, another antagonist of BMP signaling pathway, significantly decrease the frequency of miniature EPSCs. These results demonstrate that the BMP signaling pathway contributes to synaptic plasticity and learning likely through a presynaptic mechanism.
最近，人们发现几条在调节早期神经发育中起重要作用的进化保守信号通路在成体中也参与调节突触重塑。为了检测骨形态发生蛋白（BMP）信号成分在成体神经元中的表达是否在出生后调节神经元可塑性方面也发挥作用，我们通过基因敲除BMP抑制剂脊索蛋白在体内和体外调节小鼠的BMP信号，或者将重组BMP信号通路成分灌注到急性海马切片上。脊索蛋白基因敲除小鼠海马神经元的突触前递质释放显著增加，导致成对脉冲易化和长时程增强增强。这些小鼠在水迷宫试验中的习得时间也缩短，并且在Y迷宫和旷场试验中的探索活动减少。将BMP配体灌注到海马切片上可重现脊索蛋白基因敲除切片的突触前表型，但浴加另一种BMP信号通路拮抗剂头蛋白可显著降低微小兴奋性突触后电流的频率。这些结果表明，BMP信号通路可能通过突触前机制对突触可塑性和学习有贡献。
