Neural Substrates Of Stimulus Recognition And Association Memory

刺激识别和关联记忆的神经基质

• 批准号: 8745696
• 负责人: ELISABETH A MURRAY
• 金额: $ 49.94万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8745696
• 关键词: Accounting; Affect; Alzheimer' s Disease; Amnesia; Area; Association Learning; Behavior; Bilateral; Boxing; Brain; Brain Injuries; Complex; Conscious; Cues; Data; Degenerative Disorder; Development; Disease; Elements; Event; Excision; Feeling; Future; Goals; Herpes encephalitis; Hippocampus (Brain); Image; Impaired cognition; Independent Living; Infusion procedures; Knowledge; Learning; Life Experience; Location; Measures; Medial; Memory; Memory Disorders; Memory impairment; Neocortex; Paired-Associate Learning; Pathology; Pathway interactions; Patients; Pattern; Perception; Performance; Prefrontal Cortex; Procedures; Process; Relative (related person); Research; Research Design; Response to stimulus physiology; Rewards; Role; Ruptured Aneurysm; Saline; Semantic Dementias; Services; Source; Stimulus; Stream; Structure; System; Temporal Lobe; Testing; Textbooks; Thalamic structure; Therapeutic Intervention; Time; Virus Diseases; Visual; Visual Perception; Work; anterior communicating artery; base; classical conditioning; entorhinal cortex; frontal lobe; improved; inhibitor/antagonist; learned behavior; neocortical; novel; relating to nervous system; response; theories; touchscreen; visual motor; visual stimulus

Our most recent work on this project has made use of two measures of memory, both involving objects. One type of memory, known as paired associate learning, involves the arbitrary association between two different visual stimuli. A second measure of memory involves the arbitrary association between visual stimuli and spatially-directed responses, known as visuomotor conditional learning. Amnesic patients are notoriously poor in acquiring arbitrary associations, and so these kinds of behavior serve as reliable indicators of memory function. In visuomotor conditional learning, subjects are presented with one of three images on a touch screen and learn which one of three identical target boxes is correct on that trial. The target boxes appear in fixed locations. If the subject chooses the correct location cued by the image for that trial, a reward is delivered. In essence, the subjects learn that each image is associated with a particular spatially directed goal or response. Subjects learn three problems at a time in sessions with novel stimuli, called novel sessions, which because they use new stimuli require the formation of new associative memories. In addition, behavior can be compared for familiar memories, which use well learned stimuli. These sessions are called familiar sessions. In paired associate learning, subjects see images in the same way as in the visuomotor conditional learning. The difference is that they choose a target image associated with it rather than a target box in a fixed location. As in visuomotor conditional learning, behavior on novel and familiar sessions can be contrasted. There is evidence that the hippocampal system is not necessary for paired associate learning. Murray et al. (1993) found that paired associate learning was unaffected by complete removal of the hippocampus. This could mean that the hippocampal system is unnecessary for associative learning when neither component of the association has a relevant spatial attribute. But recent work on this project appears to rule out that account (Brasted et al., 2002, 2003, 2005). This research showed that hippocampal-system damage, specifically a transection of the fornix, impaired fast learning of visuomotor conditional associations even when both the visual stimuli and the responses were nonspatially differentiated. This finding points to another possibility for the results described by Murray et al. (1993). According to this explanation of our paired associate learning results, there was no deficit because subjects learned the paired associates slowly in that prior study. This hypothesis predicts that hippocampal-system damage might cause deficits in the fast learning of paired associates. Accordingly, we are engaged in testing the role of the hippocampus in paired associate learning using a fast learning procedure. This research tests a more general theory of hippocampal function, which holds that it subserves rapid acquisition, as a pattern-associator network, whereas the neocortex acquires similar information, but more slowly. In the context of paired associate learning, this theory implies that the perirhinal cortex, a neocortical area, subserves the slower form of learning and that the hippocampal system subserves the faster form. We have now developed procedures that allow subjects to acquire both visuomotor conditional and paired associations rapidly, within a single testing session. The results from this project could resolve crucial issues about hippocampal and perirhinal cortex function. A second aim of this project is to determine what part of the hippocampal system is essential for fast visuomotor conditional learning. To determine the role of the hippocampus in this task, we assessed the effects on behavior of bilateral infusions into the hippocampus of a neural inhibitor or saline. Our data indicate that there is no effect of hippocampal inactivation on visuomotor conditional learning relative to saline infusion or no infusion. For both novel and familiar sessions, hippocampal inactivation did not impair the overall performance or the rate of learning across blocks of trials. These findings suggest that regions outside the hippocampus proper, either alone or together with the hippocampus, contribute to performance on this task. Candidates include the subicular complex and the entorhinal cortex. Accordingly, we assessed the contribution to visuomotor conditional learning and performance of one other structure in the MTL, the entorhinal cortex. The entorhinal cortex is not only a major source of inputs to the hippocampus, but also has widespread projections to other cortical fields implicated in memory, including the medial prefrontal cortex. Bilateral inactivation of the entorhinal cortex impaired performance on both familiar and novel sessions, and slowed the within-session learning rate during novel sessions. A future aim of this project is to examine the role of MTL-prefrontal interactions in fast associative learning. We predict that both direct and indirect prefrontal-hippocampal connections, via the fornix and entorhinal cortex, respectively, are critical for rapid, arbitrary associative learning of both types studied in this project. If confirmed, this hypothesis could promote the development of therapeutic interventions aimed as facilitating one pathway when damage or disease disrupts the other.

我们在这个项目上的最新工作使用了两个内存度量，两者都涉及对象。一种类型的记忆称为配对联想学习，涉及两个不同视觉刺激之间的任意关联。记忆的第二个测量涉及视觉刺激和空间定向反应之间的任意联系，称为视觉运动条件学习。众所周知，健忘症患者在获得任意联想方面很差，因此这些行为是记忆功能的可靠指标。 在视觉运动条件学习中，受试者被呈现在触摸屏上的三个图像中的一个，并学习在该试验中三个相同的目标框中的哪个是正确的。目标框显示在固定位置。如果受试者选择了根据试验图像提示的正确位置，就会得到奖励。从本质上讲，受试者了解到每个图像都与特定的空间定向目标或反应相关联。受试者在使用新刺激的过程中一次学习三个问题，这被称为新的过程，因为他们使用新的刺激需要形成新的联想记忆。此外，可以将行为与熟悉的记忆进行比较，这些记忆使用了良好的学习刺激。这些会话称为熟悉会话。在配对联想学习中，受试者看到图像的方式与视觉运动条件学习中的相同。不同的是，他们选择的是与之相关联的目标图像，而不是固定位置的目标框。就像在视觉运动条件学习中一样，在新的和熟悉的会话中的行为可以被对比。 有证据表明，海马体系统不是配对联想学习所必需的。Murray等人。(1993)发现，完全移除海马体不会影响配对联想学习。这可能意味着，当联想的两个组成部分都没有相关的空间属性时，海马体系统对于联想学习来说是不必要的。但最近关于该项目的工作似乎排除了这种说法(Brasted等人，2002、2003、2005)。这项研究表明，即使在视觉刺激和反应都是非空间差异的情况下，海马体系统的损伤，特别是穹隆的横断，也会损害视觉运动条件联系的快速学习。这一发现为Murray等人描述的结果指出了另一种可能性。(1993年)。根据我们对配对联想学习结果的解释，没有出现差异，因为受试者在之前的研究中学习配对联想的速度很慢。这一假说预测，海马体系统的损伤可能会导致配对伙伴的快速学习能力受损。因此，我们正在使用快速学习程序测试海马体在配对联想学习中的作用。这项研究测试了一个关于海马体功能的更一般的理论，该理论认为，作为一个模式联想网络，它有助于快速获得，而新皮质获得类似的信息，但速度更慢。在配对联想学习的背景下，这一理论意味着，大脑周围皮质这一新皮质区域从属于较慢形式的学习，而海马体系统从属于较快形式的学习。我们现在已经开发了程序，允许受试者在一次测试中快速获得视觉运动条件联系和配对联系。该项目的结果可能解决有关海马区和大脑周围皮质功能的关键问题。 这个项目的第二个目标是确定海马体系统的哪个部分对于快速视觉运动条件学习是必不可少的。为了确定海马区在这项任务中的作用，我们评估了双侧海马区注射神经抑制剂或生理盐水对行为的影响。我们的数据表明，与生理盐水注射或不注射相比，海马区失活对视觉运动条件学习没有影响。对于新的和熟悉的过程，海马体的失活并没有损害总体表现或跨试验块的学习速度。这些发现表明，海马体之外的区域，无论是单独的还是与海马体一起的，都有助于完成这项任务。候选者包括下丘复合体和内嗅皮层。因此，我们评估了MTL中的另一个结构--内嗅觉皮质对视觉运动条件学习和表现的贡献。内嗅觉皮质不仅是海马体的主要输入来源，而且还广泛地投射到与记忆有关的其他皮质区域，包括内侧前额叶皮质。双侧内嗅皮层的失活损害了熟悉的和新的会话的表现，并减慢了新会话的会话内学习速度。 这个项目的未来目标是研究MTL-前额叶交互作用在快速联想学习中的作用。我们预测，通过穹隆和内嗅皮层的直接和间接前额-海马区联系，对于本项目所研究的两种类型的快速、任意联想学习都是至关重要的。如果得到证实，这一假说可能会促进治疗干预措施的发展，目的是在损伤或疾病扰乱另一条途径时促进另一条途径。