A key role for nectin-1 in the ventral hippocampus in contextual fear memory.
A key role for nectin-1 in the ventral hippocampus in contextual fear memory.
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DOI：
10.1371/journal.pone.0056897
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sandi C
中科院分区：
文献类型：
--
作者：
Fantin M;van der Kooij MA;Grosse J;Krummenacher C;Sandi C
连接素是广泛表达于脑中的细胞粘附分子。Nectin的表达具有动态的时空调控性，在发育过程中参与神经元的迁移过程。Nectin-1和Nectin-3及其异嗜性反式相互作用对于突触的正确形成是重要的。在海马中，nectin-1和nectin-3定位于粘附点连接处，并且可能在突触可塑性中发挥作用，这是记忆和学习所必需的机制。我们使用情绪学习范式评估了nectin-1和nectin-3在记忆巩固中的潜在参与。大鼠训练的上下文恐惧条件显示短暂的nectin-1，但不是nectin-3蛋白上调突触富集海马分数约2小时posttraining。nectin-1的上调被发现只在腹侧海马，是明显的synaptoneurosomal分数。这种上调是由上下文恐惧条件反射引起的，而不是单独暴露于上下文或休克。当针对nectin-1的抗体R165在训练后立即注入腹侧海马时，背景恐惧记忆受损。然而，在背侧海马中用抗体处理对情境恐惧记忆形成没有影响。类似地，在腹侧海马中用抗体处理不干扰声学记忆形成。进一步的对照实验表明，腹侧海马输注nectin-1抗体在情境恐惧记忆中的作用不能归因于记忆非特异性效应，例如焦虑样行为或运动行为的变化。因此，我们得出结论，nectin-1招聘到突触周围环境中的腹侧海马起着重要的作用，在形成的背景恐惧记忆。我们的研究结果表明，这些机制可能涉及在杏仁核和背侧海马，分别处理的情感和上下文信息的连接，从而开辟了新的途径，为发展治疗精神病理学改变与受损的情境化的情绪。
Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1—but not nectin-3—protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the amygdala and dorsal hippocampus, respectively, thus opening new venues for the development of treatments to psychopathological alterations linked to impaired contextualization of emotions.
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