The receptor deleted in colorectal cancer (DCC) and its ligand netrin-1 are essential for axon guidance during development and are expressed by neurons in the mature brain. Netrin-1 recruits GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and is critical for long-term potentiation (LTP) at CA3-CA1 hippocampal Schaffer collateral synapses, while conditional DCC deletion from glutamatergic neurons impairs hippocampal-dependent spatial memory and severely disrupts LTP induction. DCC co-fractionates with the detergent-resistant component of postsynaptic density, yet is enriched in axonal growth cones that differentiate into presynaptic terminals during development. Specific presynaptic and postsynaptic contributions of DCC to the function of mature neural circuits have yet to be identified. Employing hippocampal subregion-specific conditional deletion of DCC, we show that DCC loss from CA1 hippocampal pyramidal neurons resulted in deficits in spatial memory, increased resting membrane potential, abnormal dendritic spine morphology, weaker spontaneous excitatory postsynaptic activity, and reduced levels of postsynaptic adaptor and signaling proteins; however, the capacity to induce LTP remained intact. In contrast, deletion of DCC from CA3 neurons did not induce detectable changes in the intrinsic electrophysiological properties of CA1 pyramidal neurons, but impaired performance on the novel object place recognition task as well as compromised excitatory synaptic transmission and LTP at Schaffer collateral synapses. Together, these findings reveal specific pre- and post-synaptic contributions of DCC to hippocampal synaptic plasticity underlying spatial memory.

中文翻译：

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DCC在成年小鼠海马中的记忆巩固中突触前和突触后的作用。

大肠癌（DCC）中缺失的受体及其配体netrin-1对于发育过程中的轴突导向至关重要，并由成熟脑中的神经元表达。Netrin-1募集含有GluA1的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR），对于CA3-CA1海马Schaffer侧突触的长期增强（LTP）至关重要，而有条件DCC谷氨酸能神经元的缺失会损害海马依赖性空间记忆并严重破坏LTP诱导。DCC与突触后密度的耐去污剂成分共馏分，但富含轴突生长锥，在发育过程中分化为突触前末端。DCC对成熟神经回路功能的特定突触前和突触后贡献尚未确定。利用海马区域特定条件的DCC的条件性删除，我们表明，CA1海马锥体神经元的DCC丢失导致空间记忆不足，静息膜电位增加，树突棘形态异常，自发性兴奋性突触后突触活动减弱以及突触后衔接子和连接蛋白水平降低信号蛋白；但是，诱导LTP的能力保持不变。相比之下，从CA3神经元中删除DCC不会诱导CA1锥体神经元的内在电生理特性的可检测变化，但是会削弱在新颖的物体位置识别任务上的性能以及在Schaffer侧突触中损害的兴奋性突触传递和LTP。一起，