Signals to Feed: Biological and Associative Mechanisms

描述（由申请人提供）：记忆功能障碍和食物摄入调节障碍似乎没有什么共同之处，除了这两个事实都对健康和福祉有非常负面的影响。然而，新的数据和对旧发现的新解释表明，在学习和记忆的基础机制和涉及食物摄入调节的生理过程之间存在着许多有趣的联系。拟议研究的长期目标是了解这些过程是如何相互关联的。利用大鼠模型，这项工作将重点关注三种神经肽，胰岛素，瘦素和胃饥饿素，每一种都被认为向大脑提供有关身体能量资源状态的信息，每一种都似乎与海马体的功能有关，海马体是一种长期被认为是学习和记忆器官的大脑结构。在本研究的初始阶段，将使用行为范式来评估这些神经肽通过(a)产生内感受性饥饿或饱腹感刺激（如禁食或随意进食时产生的刺激）对食物摄入调节的影响程度；(b)改变进食的感官后果；(c)改变进食后的食后影响和/或；(d)作为预测信号，预示特定的口腔感觉或进食后后果可能发生。其次，本研究将利用海马在食物摄入调节中的作用。海马体选择性神经毒性损伤对摄入调节的学习控制和生理控制的影响将被评估。第三，本研究将开始系统地研究食物摄入调节过程介导海马依赖学习和记忆功能表现的可能性。这些实验的目的是确定胰岛素缺乏或胰岛素抵抗的大鼠在不同的学习和记忆任务中是否表现出与没有海马体的大鼠相似的损伤模式。希望本文提出的研究将使我们能够识别控制学习记忆和食物摄入调节的共同神经和联想基础。发现这些机制是如何相互联系的，对于理解、诊断和治疗记忆和能量调节障碍具有重要意义。

DESCRIPTION (provided by applicant): Disorders of memory function and of food intake regulation may seem to have little in common, except for the fact that both can have very negative effects on health and well-being. Yet, new data and new interpretations of older findings, suggest the existence of a number of intriguing links between the mechanisms that underlie learning and memory and the physiological processes involved with food intake regulation. The long-term goal of the proposed research is to understand how these processes are interrelated. Using a rat model, this work will focus on three neuropetides, insulin, leptin, and ghrelin, each of which have been proposed to provide information to the brain about the status of bodily energy resources, and each of which appears to be involved with the function of the hippocampus, a brain structure long considered to be an organ of learning and memory. In the initial phase of this research, behavioral paradigms will be used that can assess the extent to which these neuropeptides influence food intake regulation by (a) producing interoceptive hunger or satiety stimuli like those produced by periods of fasting or ad lib feeding; (b) altering the orosensory consequences of eating;(c) altering the post-ingestive after affects of eating and/or; (d) serving as predictive signals for when particular orosensory or post-ingestive consequences are likely to occur. Secondly, this research will use the role of the hippocampus in food intake regulation. The effects of selective neurotoxic lesions of the hippocampus on the learned and physiological controls of intake regulation will be evaluated. Thirdly, this research will begin to study systematically the possibility that processes involved with food intake regulation mediate the performance of hippocampal-dependent learning and memory functions. The goal of these experiments will be to determine if rats that have been made insulin-deficient or insulin-resistant show patterns of impairment on different learning and memory tasks that are like those shown by rats without a hippocampus. It is hoped that the research proposed here will enable us to identify common neural and associative bases for the control of learning and memory and food intake regulation. Discovery of how these mechanisms are interconnected should have important implications for understanding, diagnosing, and treating disorders of both memory and energy regulation.