Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Neuron. 2010 Dec 9;68(5):894-906. doi: 10.1016/j.neuron.2010.11.003.
Synaptogenesis is required for wiring neuronal circuits in the developing brain and continues to remodel adult networks. However, the molecules organizing synapse development and maintenance in vivo remain incompletely understood. We now demonstrate that the immunoglobulin adhesion molecule SynCAM 1 dynamically alters synapse number and plasticity. Overexpression of SynCAM 1 in transgenic mice promotes excitatory synapse number, while loss of SynCAM 1 results in fewer excitatory synapses. By turning off SynCAM 1 overexpression in transgenic brains, we show that it maintains the newly induced synapses. SynCAM 1 also functions at mature synapses to alter their plasticity by regulating long-term depression. Consistent with these effects on neuronal connectivity, SynCAM 1 expression affects spatial learning, with knock-out mice learning better. The reciprocal effects of increased SynCAM 1 expression and loss reveal that this adhesion molecule contributes to the regulation of synapse number and plasticity, and impacts how neuronal networks undergo activity-dependent changes.
突触发生对于发育中大脑中的神经元回路的布线是必需的，并且会继续重塑成年网络。然而，在体内组织突触发生和维持的分子仍不完全清楚。我们现在证明免疫球蛋白黏附分子 SynCAM1 可以动态改变突触数量和可塑性。在转基因小鼠中过表达 SynCAM1 会促进兴奋性突触数量增加，而 SynCAM1 的缺失则导致兴奋性突触数量减少。通过在转基因大脑中关闭 SynCAM1 的过表达，我们表明它维持了新诱导的突触。SynCAM1 还在成熟的突触中发挥作用，通过调节长时程抑制来改变它们的可塑性。与神经元连接的这些影响一致，SynCAM1 的表达影响空间学习，敲除小鼠学习能力更好。SynCAM1 表达增加和缺失的相互作用表明，这种黏附分子有助于调节突触数量和可塑性，并影响神经元网络如何发生依赖于活动的变化。
