情境恐惧条件反射后,背侧海马中多唾液酸化神经细胞黏附分子的上调参与长期记忆形成。
Upregulation of polysialylated neural cell adhesion molecule in the dorsal hippocampus after contextual fear conditioning is involved in long-term memory formation.
作者信息
Lopez-Fernandez Miguel A, Montaron Marie-Françoise, Varea Emilio, Rougon Genevieve, Venero Cesar, Abrous Djoher Nora, Sandi Carmen
机构信息
Brain Mind Institute, Swiss Federal Institute of Technology, CH-1015 Lausanne, Switzerland.
出版信息
J Neurosci. 2007 Apr 25;27(17):4552-61. doi: 10.1523/JNEUROSCI.0396-07.2007.
The role of the hippocampus in pavlovian fear conditioning is controversial. Although lesion and pharmacological inactivation studies have suggested a key role for the dorsal hippocampus in contextual fear conditioning, the involvement of the ventral part is still uncertain. Likewise, the debate is open with regard to the putative implication of each hippocampal subdivision in fear conditioning to a discrete conditioned stimulus. We explored the potential existence of dissociations occurring in the dorsal versus ventral hippocampus at the cellular level while dealing with either contextual or cued fear conditioning and focused in a molecular "signature" linked to structural plasticity, the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). We found an upregulation of PSA-NCAM expression in the dorsal (but not ventral) dentate gyrus at 24 h after contextual (but not tone) fear conditioning. Specific removal of PSA through microinfusion of the enzyme endoneuraminidase-N in the dorsal (but not ventral) hippocampus reduced freezing responses to the conditioned context. Therefore, we present evidence for a specific role of PSA-NCAM in the dorsal hippocampus in the plasticity processes occurring during consolidation of the context representation after "standard" contextual fear conditioning. Interestingly, we also found that exposing animals just to the context induced an activation of PSA-NCAM in both dorsal and ventral dentate gyrus. Altogether, these findings highlighting the distinctive occurrence of these neuroplastic processes in the dorsal hippocampus during the standard contextual fear-conditioning task enlighten the ongoing debate about the involvement of these hippocampal subdivisions in pavlovian fear conditioning.
海马体在巴甫洛夫恐惧条件反射中的作用存在争议。尽管损伤和药理学失活研究表明背侧海马体在情境恐惧条件反射中起关键作用,但腹侧部分的参与情况仍不确定。同样,关于海马体各亚区在对离散条件刺激的恐惧条件反射中的假定作用,争论也尚未定论。我们探讨了在处理情境性或线索性恐惧条件反射时,背侧与腹侧海马体在细胞水平上是否存在分离,并聚焦于与结构可塑性相关的分子“特征”——神经细胞黏附分子的多唾液酸化形式(PSA-NCAM)。我们发现在情境性(而非音调)恐惧条件反射后24小时,背侧(而非腹侧)齿状回中PSA-NCAM表达上调。通过向背侧(而非腹侧)海马体微量注射神经氨酸酶-N特异性去除PSA,可降低对条件化情境的僵住反应。因此,我们提供了证据表明,在“标准”情境性恐惧条件反射后,情境表征巩固过程中发生的可塑性过程中,PSA-NCAM在背侧海马体中具有特定作用。有趣的是,我们还发现仅让动物暴露于情境中会导致背侧和腹侧齿状回中PSA-NCAM的激活。总之,这些发现在标准情境性恐惧条件反射任务中突出了背侧海马体中这些神经可塑性过程的独特发生情况,为正在进行中的关于这些海马体亚区在巴甫洛夫恐惧条件反射中所起作用的争论提供了启示。