Retrograde amnesia after hippocampal damage

描述（由申请人提供）：记忆障碍可能是任何破坏正常内侧颞叶功能的过程后最常见的症状。最严重的失忆症包括丧失形成新记忆的能力（顺行性失忆症）和丧失受损前的记忆（逆行性失忆症）。提出了三个大鼠实验，以解决逆行性健忘症的神经机制的基本特性。第一项研究评估了由多次微量注射n -甲基-天冬氨酸引起的几乎完全的、选择性的海马形成损伤所产生的逆行性遗忘的时间依赖性。使用受试者间和受试者内设计，我们评估了4种类型信息的逆行性遗忘的严重程度：空间地图、语境条件反射、结构歧视和社会传播的饮食偏好。在训练和海马损伤之间的几个间隔取样，在1到64周之间。此外，我们独立测试了远程学习时记忆再激活和被试年龄的影响。其次，我们比较了逆行缺陷和逆行缺陷对某些类型信息的选择性。顺行性健忘症影响陈述性/关系性/构形性信息，而不影响非陈述性/非关系性/基本信息。利用莫里斯水任务、巴甫洛夫恐惧条件反射、社会传递饮食偏好和横向模式等4个任务的变体，我们研究了海马损伤后逆行性失忆症的这种区别。第三，我们使用不同数量的NMDA和秋水仙碱齿状回显微注射，比较不同程度海马损伤的逆行梯度和任务特异性。这些比较将解决以下假设：逆行性失忆症的时间梯度与保留的海马体回路的数量有关，而齿状回回路仅在初始记忆获取时起作用。这一结果与海马体依赖的长期记忆巩固理论的基本方面有关，并将更准确地描述海马体形成在长期记忆中的作用。

DESCRIPTION (provided by applicant): Memory disorders are probably the most common symptom after any process that disrupts normal medial temporal lobe functioning. The most severe form of disorder involves the loss of ability to form new memories (anterograde amnesia) and the loss of memories from before the damage (retrograde amnesia). Three experiments with rats are proposed which address fundamental properties of the neural mechanisms of retrograde amnesia. The first evaluates the temporal dependence of retrograde amnesia produced by nearly complete, selective hippocampal formation damage caused by multiple microinjections of N-methyl-Daspartate. Using both a between- and within-subject design, we evaluate the severity of retrograde amnesia for 4 types of information, spatial map, contextual conditioning, configural discriminations, and socially transmitted diet preference. Several intervals between training and hippocampal damage are sampled, between 1 and 64 weeks. Further, we independently test the effects of memory reactivations and subject age at the time of remote learning. Second, we compare the selectivity of the retrograde deficits with anterograde deficits for certain types of information. Anterograde amnesia affects declarative/relational/configural information and not nondeclarative/nonrelational/elemental information. Using variants of 4 tasks involving Morris water task, Pavlovian fear conditioning, socially transmitted diet preference, and transverse patterning we examine this distinction in retrograde amnesia after hippocampal damage. Third, we compare the retrograde gradients and the task specificity with different extents of hippocampal damage, using varying numbers of NMDA microinjections and colchicine dentate gyrus microinjections. The comparisons will address the hypotheses that temporal gradients in retrograde amnesia are related to the amount of spared hippocampal circuitry and that dentate gyrus circuitry contributes only at the time of initial memory acquisition. The results bear upon fundamental aspects of hippocampal dependent, long-term memory consolidation theories and will delineate a more precise role for the hippocampus formation in long-term memory.