Center for Neuroscience, University of California, Davis, CA 95616, USA.
Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):E305-12. doi: 10.1073/pnas.1214705110. Epub 2012 Dec 26.
Refinement of neural circuits in the mammalian cerebral cortex shapes brain function during development and in the adult. However, the signaling mechanisms underlying the synapse-specific shrinkage and loss of spiny synapses when neural circuits are remodeled remain poorly defined. Here, we show that low-frequency glutamatergic activity at individual dendritic spines leads to synapse-specific synaptic weakening and spine shrinkage on CA1 neurons in the hippocampus. We found that shrinkage of individual spines in response to low-frequency glutamate uncaging is saturable, reversible, and requires NMDA receptor activation. Notably, shrinkage of large spines additionally requires signaling through metabotropic glutamate receptors (mGluRs) and inositol 1,4,5-trisphosphate receptors (IP(3)Rs), supported by higher levels of mGluR signaling activity in large spines. Our results support a model in which signaling through both NMDA receptors and mGluRs is required to drive activity-dependent synaptic weakening and spine shrinkage at large, mature dendritic spines when neural circuits undergo experience-dependent modification.
哺乳动物大脑皮层中的神经回路的精细化塑造了发育过程中和成年期的大脑功能。然而，当神经回路重塑时，导致棘突突触特异性收缩和丢失的信号机制仍未得到很好的定义。在这里，我们表明，单个树突棘上的低频谷氨酸能活动导致海马体 CA1 神经元上棘突突触的特异性突触减弱和棘突收缩。我们发现，单个棘突对低频谷氨酸释放的反应是可饱和的、可逆的，并且需要 NMDA 受体的激活。值得注意的是，大棘突的收缩还需要通过代谢型谷氨酸受体 (mGluRs) 和肌醇 1,4,5-三磷酸受体 (IP(3)Rs) 进行信号传递，这得到了大棘突中更高水平的 mGluR 信号传递活性的支持。我们的结果支持这样一种模型，即在神经回路经历经验依赖性修饰时，需要通过 NMDA 受体和 mGluRs 进行信号传递，以驱动大而成熟的树突棘上的活性依赖性突触减弱和棘突收缩。
