Retrograde Amnesia for Trace Fear Conditioning

大脑如何从环境中提取信息并将其存储为记忆，这是行为神经科学中一个基本但尚未回答的问题。在人类和其他动物中，与记忆关系最密切的大脑结构是海马体。大脑这一区域的损伤会导致健忘症或记忆力丧失，这在所有哺乳动物中都有许多共同特征。本项目关注其中的两个共性。其中之一是，在海马区受损前不久获得的记忆丢失了，但较旧的记忆仍然存在。这种记忆丧失的模式被称为时间渐进性逆行性健忘症。在对大鼠进行了一项通常不会被遗忘的任务的训练后，通过对海马体进行非常精确的损伤来检查大鼠的逆行性健忘症。这项任务是恐惧条件反射，老鼠对之前预测它们将受到短暂的轻微电击的刺激表现出情绪反应。由海马体损伤引起的健忘症的另一个特征是，某些类型的记忆丢失，而其他类型的记忆完全幸免。例如，如果向海马区受损的人传授一种新的运动技能，如网球，他们的网球比赛能力将不断提高，但他们将失去打过网球的记忆。他们记得如何打球，却不记得自己打过球。我们将研究这种选择性记忆丧失的一种形式。如果音调预示休克，海马区的损伤可能会也可能不会导致遗忘症，因为音调和习得的情绪之间的关系。如果音调和电击在时间上重叠，海马体就没有必要了。然而，如果在音调终止和电击发作之间有一段很短的时间，海马体是记忆所必需的。这种类型的条件反射被称为痕迹条件反射，在海马区受损后，我们将检查痕迹条件反射的逆行性遗忘。痕迹条件反射的健忘症是不寻常的，因为它不同于其他形式的记忆，需要海马体来实现。通常，海马区受损的大鼠对空间位置或由几个不同成分组成的刺激的记忆存在问题。在这个项目中，将确定痕迹条件反射和复杂结构的逆行性健忘症是否源于海马体的相同或不同功能。还将确定各种改变正常动物学习痕迹条件作用的能力的手法是否可以减轻对痕迹条件作用的健忘症。通过研究和对比这些形式的记忆，人们希望准确地找到海马体从经验中提取什么，并更准确地确定在健忘症中丢失和保存的是什么。

How the brain extracts information to from the environment and stores that information as a memory is a fundamental but unanswered question in behavioral neuroscience. The brain structure that is most intimately associated with memory in humans and other animals is the hippocampus. Damage to this brain area produces amnesia, or loss of memory, that shares many features in all mammals. This project focuses on two of these commonalties. One is that memories that were acquired shortly before hippocampal damage are lost but older memories remain. This pattern of memory loss is called temporally graded retrograde amnesia. Retrograde amnesia in rats will be examined by making very precise damage to the hippocampus after various times after rats are trained on a task that is not normally forgotten. The task is fear conditioning, where rats show an emotional reaction to stimuli that have previously predicted that they will receive a brief mild electric footshock.Another feature of the amnesia that stems from hippocampal damage is that certain types of memories are lost and others are completely spared. For example, if people with hippocampal damage are taught a new motor skill like tennis, their tennis playing ability will continual improve but they will have no memory of ever playing tennis. They remember how to play without being able to remember that they played. One form of this selective memory loss will be examined. If a tone predicts shock, hippocampal lesions may or may not cause amnesia for the relation between tone and the learned emotion. If the tone and shock overlap in time the hippocampus is not necessary. However, if a brief period of time is placed between tone termination and shock onset the hippocampus is necessary for memory. This type of conditioning is called trace conditioning and retrograde amnesia for trace conditioning following hippocampal damage will be examined.Amnesia for trace conditioning is unusual because it differs from other forms of memory for which the hippocampus is needed. Usually rats with hippocampal damage have problems with memory for spatial locations or for stimuli that are composed of several different components. In this project it will be determined whether retrograde amnesia for trace conditioning and complex configurations stem from the same or different functions of the hippocampus. It will also be determined if various manipulations that alter the ability of normal animals to learn trace conditioning can alleviate the amnesia for trace conditioning. By investigating and contrasting these forms of memory it is hoped to find exactly what the hippocampus is extracting from experience and more precisely define what is lost and preserved in amnesia.