DCC Expression by Neurons Regulates Synaptic Plasticity in the Adult Brain
DCC Expression by Neurons Regulates Synaptic Plasticity in the Adult Brain
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DOI：
10.1016/j.celrep.2012.12.005
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发表时间：
2013-01-01
期刊：
影响因子：
8.8
通讯作者：
Kennedy, Timothy E.
中科院分区：
文献类型：
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作者：
Horn, Katherine E.;Glasgow, Stephen D.;Kennedy, Timothy E.
结直肠癌（DCC）中缺失的跨膜蛋白及其配体netrin-1在发育过程中调节突触发生，但它们在成熟中枢神经系统中的功能尚不清楚。考虑到DCC促进细胞间粘附，由神经元表达，并激活突触信号蛋白，我们假设神经元表达DCC调节成人大脑突触功能和可塑性。我们报道了DCC在野生型小鼠锥体神经元的树突棘中丰富，并且我们证明了成人前脑神经元中DCC的选择性删除导致长期增强（LTP）的丧失，完整的长期抑制，更短的树突棘，以及空间和识别记忆受损。LTP的诱导需要Src激活NMDA受体（NMDAR）功能。DCC的删除严重降低了Src的激活。我们证明，在没有DCC的情况下，增强NMDAR功能或激活Src可以挽救LTP。我们得出结论，DCC激活Src对于nmdar依赖的LTP和某些形式的学习和记忆是必需的。
The transmembrane protein deleted in colorectal cancer (DCC) and its ligand, netrin-1, regulate synaptogenesis during development, but their function in the mature central nervous system is unknown. Given that DCC promotes cell-cell adhesion, is expressed by neurons, and activates proteins that signal at synapses, we hypothesized that DCC expression by neurons regulates synaptic function and plasticity in the adult brain. We report that DCC is enriched in dendritic spines of pyramidal neurons in wild-type mice, and we demonstrate that selective deletion of DCC from neurons in the adult forebrain results in the loss of long-term potentiation (LTP), intact long-term depression, shorter dendritic spines, and impaired spatial and recognition memory. LTP induction requires Src activation of NMDA receptor (NMDAR) function. DCC deletion severely reduced Src activation. We demonstrate that enhancing NMDAR function or activating Src rescues LTP in the absence of DCC. We conclude that DCC activation of Src is required for NMDAR-dependent LTP and certain forms of learning and memory.