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。最严重的疾病形式包括丧失形成新记忆的能力（顺行性遗忘症）和丧失损伤前的记忆（逆行性遗忘症）。提出了三个大鼠实验，解决逆行性遗忘症的神经机制的基本特性。第一个评估的时间依赖性逆行性遗忘所产生的几乎完全的，选择性海马结构损伤所造成的多次微量注射N-甲基-D天冬氨酸。使用之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，上下文条件反射，神经歧视，和社会传播的饮食偏好的逆行性遗忘症的严重程度。在训练和海马损伤之间的几个时间间隔取样，在1和64周之间。此外，我们独立测试的影响，记忆再激活和受试者的年龄在远程学习的时间。其次，我们比较了逆行性缺陷与顺行性缺陷对某些类型信息的选择性。顺行性遗忘症影响陈述性/关系性/记忆性信息，而不影响非陈述性/非关系性/基本信息。使用4个任务的变体，包括Morris水任务，巴甫洛夫恐惧条件反射，社会传播的饮食偏好，和横向图案，我们研究这种区别在海马损伤后的逆行性遗忘。第三，我们比较了逆行梯度和任务特异性与不同程度的海马损伤，使用不同数量的NMDA显微注射和秋水仙碱齿状回显微注射。比较将解决的假设，逆行性遗忘症的时间梯度与备用海马电路的数量和齿状回电路的贡献，只有在最初的记忆采集的时间。这些结果与海马依赖性的长期记忆巩固理论的基本方面有关，并将描绘海马形成在长期记忆中的更精确的作用。

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.