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取调节障碍似乎几乎没有共同点，除了这两者都可能对健康和福祉产生非常负面的影响这一事实。然而，新的数据和对旧发现的新解释表明，在构成学习和记忆基础的机制和涉及食物摄取调节的生理过程之间存在着一些有趣的联系。拟议研究的长期目标是了解这些过程是如何相互关联的。使用大鼠模型，这项工作将集中在三个神经肽，胰岛素，瘦素和Ghrelin，每一个都被提出向大脑提供关于身体能量资源状况的信息，并且每一个似乎都与海马体的功能有关，海马体是一个大脑结构，长期以来被认为是学习和记忆的器官。在这项研究的初始阶段，将使用行为范式来评估这些神经肽在以下方面影响食物摄入量的程度：(A)产生感觉间的饥饿或饱腹感刺激，如禁食或随意喂养时期产生的那种刺激；(B)改变进食的或感觉的后果；(C)改变进食和/或进食的后遗症；(D)作为预测信号，指示何时可能发生特定的味觉或摄食后后果。其次，本研究将利用海马体在食物摄入量调节中的作用。我们将评估选择性海马区神经毒性损伤对习得性和生理性摄入量调节的影响。第三，本研究将开始系统地研究食物摄取调节过程调节海马区依赖的学习和记忆功能的可能性。这些实验的目的将是确定胰岛素缺乏或胰岛素抵抗的大鼠是否在不同的学习和记忆任务中表现出损害的模式，就像没有海马体的大鼠所表现的那样。希望本文提出的研究将使我们能够确定共同的神经和联系基础，以控制学习和记忆以及食物摄取调节。发现这些机制是如何相互联系的，应该对理解、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.