Neurobiology Section, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):367-72. doi: 10.1073/pnas.1015163108. Epub 2010 Dec 20.
The establishment of neuronal circuits relies on the stabilization of functionally appropriate connections and the elimination of inappropriate ones. Here we report that postsynaptic AMPA receptors play a critical role in regulating the stability of glutamatergic synapses. Removal of surface AMPA receptors leads to a decrease in the number and stability of excitatory presynaptic inputs, whereas overexpression increases synapse number and stability. Furthermore, overexpression of AMPA receptors along with Neuroligin-1 in 293T cells is sufficient to stabilize presynaptic inputs from cortical neurons onto heterologous cells. The stabilization of presynaptic inputs by AMPA receptors is not dependent on receptor-mediated current and instead relies on structural interactions mediated by the N-terminal domain of the glutamate receptor 2 (GluR2) subunit. These observations indicate that transsynaptic signaling mediated by the extracellular domain of GluR2 regulates the stability of presynaptic terminals.
神经元回路的建立依赖于功能合适的连接的稳定和不合适连接的消除。在这里，我们报告说，突触后 AMPA 受体在调节谷氨酸能突触的稳定性方面起着关键作用。去除表面 AMPA 受体导致兴奋性突触前输入的数量和稳定性下降，而过表达则增加突触数量和稳定性。此外，在 293T 细胞中过表达 AMPA 受体和 Neuroligin-1 足以稳定皮质神经元到异源细胞的突触前输入。AMPA 受体对突触前输入的稳定不依赖于受体介导的电流，而是依赖于由谷氨酸受体 2 (GluR2)亚基的 N 端结构域介导的结构相互作用。这些观察结果表明，由 GluR2 胞外结构域介导的突触间信号转导调节突触前末梢的稳定性。
