Retrograde amnesia after hippocampal damage

描述(申请人提供)：记忆障碍可能是在任何扰乱正常内侧颞叶功能的过程后最常见的症状。最严重的障碍形式包括丧失形成新记忆的能力(顺行性健忘症)和损伤前的记忆丧失(逆行性健忘症)。用大鼠进行了三个实验，这些实验解决了逆行性遗忘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-D-天冬氨酸导致的几乎完全的、选择性的海马结构损伤所产生的逆行性健忘症的时间依赖性。使用受试者间和受试者内的设计，我们评估了4种类型的信息、空间地图、语境制约、结构歧视和社会传递的饮食偏好的逆行性遗忘的严重性。训练和海马区损伤之间的几个间隔被抽样，从1周到周。此外，我们独立测试了远程学习时记忆重新激活和受试者年龄的影响。其次，对于某些类型的信息，我们比较了逆行缺陷和顺行缺陷的选择性。顺行性健忘症影响陈述性/关系性/配置性信息，而不影响非陈述性/非关系性/元素信息。使用4种任务的变体，包括Morris水任务、巴甫洛夫恐惧条件作用、社会传递的饮食偏好和横向模式，我们研究了海马区损伤后逆行性遗忘的这种区别。第三，我们使用不同数量的NMDA微量注射和秋水仙碱齿状回微量注射，比较了不同程度的海马区损伤的逆行梯度和任务特异性。这些比较将解决这样的假设，即逆行性健忘症的时间梯度与海马区备用回路的数量有关，而齿状回回路只在最初记忆获得时起作用。这些结果涉及到海马体依赖的长期记忆巩固理论的基本方面，并将描绘出海马体结构在长期记忆中更精确的作用。

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.