Forebrain circuits and control of feeding behavior by learned cues

描述(申请人提供)：食欲和进食不仅由能量需求驱动，也由与能量平衡无关的外在(环境)因素驱动。环境信号，包括习得的线索，可以在饱和状态下刺激进食，或在饥饿状态下抑制进食，从而超越体内平衡信号。这项拟议研究的长期目标是确定潜在神经回路的功能组织。我们使用了一个啮齿动物模型来进行线索诱导进食，在这个模型中，先前在动物饥饿时与食物配对的环境线索可以在饱食的大鼠中启动进食。进食增加是通过联想学习获得的其他中性信号获得的动机属性的结果。该模型提供了一个框架，以研究环境线索如何与功能前脑网络中的自我平衡信号相结合，以及这些网络是如何被经验调制的。这项拟议的研究建立在证据的基础上，即网络组成部分包括前脑、杏仁核和前额叶皮质中对联想学习和决策至关重要的区域，以及外侧下丘脑，后者是摄食、奖励和动机的整合部分。有两个独立的、相互关联的特定目标，共同研究神经系统，来自环境的信号通过这些神经系统控制摄食行为。第一个目标是确定杏仁核和前额叶皮质子系统在学习线索诱导的摄食中的作用，并确定允许学习线索与体内平衡系统整合的下丘脑底物。第二个目标是绘制支持食物与食物配对学习的网络可塑性。拟议的目标将通过行为和神经系统分析的组合来实现，其中包括选择性神经毒性损伤、解剖路径追踪和即刻早期基因(IEGs)成像。IEGs方法将包括映射单个事件(c-fos蛋白诱导)的神经元反应，以及映射时间上安排的两个事件(Arc/Arg3.1 mRNA诱导)的神经元一致激活。在这项应用中的研究计划下的工作将扩大我们对大脑回路的理解，该回路允许学习调节进食行为。研究结果还将有助于控制人类的食欲，包括可能导致暴饮暴食和肥胖的不适应环境影响。 与公共健康相关：该提案的长期目标是确定神经系统，来自环境的信号通过这些神经系统控制摄食行为。这一结果将有助于控制人类的食欲，包括可能导致调节失调、暴饮暴食和肥胖的不适应环境影响。

DESCRIPTION (provided by applicant): Appetite and eating are not only driven by energy needs, but also by extrinsic (environmental) factors unrelated to energy balance. Environmental signals, including learned cues, can override homeostatic signals to stimulate eating in sated states, or inhibit eating in states of hunger. The long-term goal of the proposed research is to define the functional organization of the underlying neural circuits. We use a rodent model for cue-induced eating, in which an environmental cue previously paired with food when an animal was hungry can initiate eating in sated rats. The enhanced eating is a consequence of motivational properties acquired by an otherwise neutral signal through associative learning. The model provides a framework to study how environmental cues are integrated with homeostatic signals within functional forebrain networks, and how these networks are modulated by experience. The proposed research builds on evidence that the network components include areas in the forebrain, amygdala and prefrontal cortex critical for associative learning and decision-making, and the lateral hypothalamus, which is an integrator for feeding, reward and motivation. There are two independent, interrelated specific aims that collectively investigate the neural systems through which signals from the environment control feeding behavior. The first aim is to define the role of the amygdala, and prefrontal cortex subsystems in learned cue-induced feeding, and to identify the hypothalamic substrates that allow learned cue integration with the homeostatic system. The second aim is to map network plasticity that supports learning underling cue-food pairing. The proposed goals will be accomplished with a combination of behavioral and neural systems analysis that include selective neurotoxic lesions, anatomical pathway tracing, and imaging with immediate early genes (IEGs). The IEGs methods will include mapping of neuronal responses to a single event (c-fos protein induction), and mapping of neuronal coincident activation by two events that are temporally arranged (Arc/Arg3.1 mRNA induction). The work under the research plan in this application will extend our understanding of the brain circuitry that allows learning to modulate feeding behavior. The results will be also informative for control of appetite in humans including maladaptive environmental influences that could contribute to overeating and obesity. PUBLIC HEALTH RELEVANCE: The long-term goal of the proposal is to identify the neural systems through which signals from the environment control feeding behavior. The results will be informative for control of appetite in humans including maladaptive environmental influences that could contribute to dysregulation, overeating and obesity.