Hippocampus, Posterior Cingulate Cortex and Contextual Learning and Memory

描述(申请人提供)：本提案旨在了解学习和记忆的神经机制。大量文献记载了海马体和后扣带回皮质在记忆功能中的作用。这些脑区的损伤与阿尔茨海默病、与年龄相关的记忆力下降以及各种人类遗忘症和学习障碍的记忆障碍有关。了解这些系统是如何工作的，对于为患有这些疾病的患者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文献记载，尽管还没有得到广泛的研究，但众所周知，后扣带回皮质在学习和记忆中也发挥着关键作用。然而，这些大脑区域中的每一个在学习过程中的确切贡献仍不清楚。最近的发现表明，这两个紧密相连的结构形成了一个功能回路，调节背景学习，但每个区域对学习过程都有不同的贡献。特定于背景的神经元放电模式的发现表明，海马体产生了背景的神经表征。相反，神经元对离散线索的反应表明，后扣带皮质编码行为上有意义的线索，包括那些唯一识别上下文的线索。这两个区域协同起到调节背景学习和记忆的作用。然而，每个大脑区域的相对贡献应该取决于手头的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，RAT将接受各种语境学习任务的培训，这些任务具有不同的线索和语境处理要求。在整个学习过程中，在海马区和后扣带回皮质都会记录到神经元的活动。暂时性的大脑神经化学损伤将被用来使每个大脑区域失效，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扰乱另一个区域的处理。通过监测受试者学习过程中神经元反应的变化以及暂时性损伤电路的影响，将有可能确定每个大脑区域处理的记忆相关信息类型，以及它们的相互作用如何产生特定于背景的记忆。 公共健康相关性：这项研究与公共健康相关，因为它调查了大脑的学习和记忆系统，特别是海马体和后扣带皮质。这些脑区的损伤与阿尔茨海默病、与年龄相关的记忆力下降以及各种其他健忘症和学习障碍的记忆障碍有关。了解这些系统是如何工作的，对于为患有这些疾病的患者制定治疗策略至关重要。

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.