Hippocampus, Posterior Cingulate Cortex and Contextual Learning and Memory

描述（由申请人提供）：本提案旨在了解学习和记忆的神经机制。大量文献记录了海马体和后扣带皮层在记忆功能中的作用。这些大脑区域的损伤与阿尔茨海默氏症、与年龄相关的记忆衰退以及各种人类健忘症和学习障碍等记忆障碍有关。了解这些系统的工作原理对于制定治疗策略至关重要。海马体的记忆作用已经有了很好的记录，尽管还没有得到广泛的研究，但人们也知道后扣带皮层在学习和记忆中起着至关重要的作用。然而，这些大脑区域对学习过程的确切贡献尚不清楚。最近的研究结果表明，这两个紧密相连的结构形成了一个功能回路，介导情境学习，但每个区域在学习过程中都有不同的贡献。情境特异性神经元放电模式的发现表明，海马体产生对情境的神经表征。相反，神经元对离散线索的反应表明，后扣带皮层对行为重要线索进行编码，包括那些唯一识别上下文的线索。这两个区域协同作用，调解上下文学习和记忆。然而，每个大脑区域的相对贡献应该取决于手头任务需要处理上下文信息或离散线索的程度。为了检验这一点，我们将对大鼠进行各种情境学习任务的训练，这些任务具有不同的线索和情境处理要求。在学习过程中，海马和后扣带皮层的神经元活动都会被记录下来。暂时的神经化学脑损伤将用于使每个大脑区域丧失功能，这样就有可能确定每个大脑区域对学习的具体贡献，并确定一个区域的丧失如何破坏另一个区域的处理。通过监测实验对象学习时神经元反应的变化，以及暂时性损伤对神经回路的影响，我们将有可能确定每个大脑区域处理了哪些与记忆相关的信息，以及它们之间的相互作用如何产生特定情境的记忆。

DESCRIPTION (provided by applicant): This proposal is aimed at understanding the neural mechanisms of learning and memory. An extensive literature has documented the role of the hippocampus and the posterior cingulate cortex in memory functions. Damage to these brain regions has been linked to the memory impairments seen in Alzheimer's disease, age-related memory decline and various human amnesic syndromes and learning disabilities. Understanding how these systems work is crucial for the development of treatment strategies for patients with these conditions. The memory role of the hippocampus has been well documented and, although it has not been studied as extensively, the posterior cingulate cortex is also known to play a critical role in learning and memory. However, the precise contribution of each of these brain regions to the learning process remains unclear. Recent findings suggest that these two closely interconnected structures form a functional circuit which mediates contextual learning, but that each region makes a distinct contribution to the learning process. Findings of context-specific neuronal firing patterns suggest that the hippocampus generates a neural representation of the context. In contrast, neuronal responses to discrete cues suggest that the posterior cingulate cortex encodes behaviorally significant cues, including those cues that uniquely identify the context. These two regions function cooperatively to mediate contextual learning and memory. However, the relative contribution of each brain region should depend on the degree to which the task at hand requires the processing of contextual information or discrete cues. To examine this, rats will be trained on various contextual learning tasks which have differing cue- and context processing requirements. Neuronal activity will be recorded in both the hippocampus and posterior cingulate cortex throughout learning. Temporary neurochemical brain lesions will be used to disable each brain region, so that it will be possible to identify the specific contribution of each brain region to learning and to determine how the loss of one region disrupts processing in the other region. By monitoring the changes in neuronal responses as subjects learn and the effects of temporary damage to the circuit, it will be possible to determine what kinds of memory related information is processed in each brain region and how their interactions yield context-specific memories. PUBLIC HEALTH RELEVANCE: This research is relevant to public health because it investigates the learning and memory systems of the brain, particularly the hippocampus and posterior cingulate cortex. Damage to these brain regions has been linked to the memory impairments seen in Alzheimer's disease, age-related memory decline and various other amnesic syndromes and learning disabilities. Understanding how these systems work is crucial for the development of treatment strategies for patients with these conditions.