Neural Basis of Motivated Behaviors

描述（由申请人提供）：实际上，每个产生复杂行为的神经回路都是一个多任务网络：它产生的不是一个行为，而是多个行为。我们在这个提议中要解决的基本问题是，是什么赋予了单个网络（中央模式生成器；CPG）产生多种行为并在它们之间切换的能力。我们建议在模型系统应用中，以咬、吞咽和排泄三种摄食行为为背景来研究这个问题。每一种行为都是由不同的高阶神经元发起的，这些神经元含有不同的神经肽补体。利用电生理、生化和分子技术的结合，我们提出测试一系列假设。首先，我们将测试这样一个假设，即每个高阶神经元通过不同程度地激活来自同一网络的单个中间神经元来引发不同的行为。由此可见，构成CPG的单个中间神经元在它们完成的功能角色上一定是不同的。我们提出了一种方案来分析单个中间神经元在产生不同行为中的作用。我们建议测试这样一个假设，即这些角色的差异源于神经元使用不同的小分子递质，这些递质可以发挥快速和缓慢的作用。最后，我们提出了一个假设，即神经元间放电模式、突触连接的可塑性和它们所利用的递质的特性的结合，有助于抵消在需要激发新行为时对先前行为的记忆可能产生的不适应方面。对以往经历的不适应的持久记忆形式可能是强迫症和抑郁症等严重行为疾病的基础。

DESCRIPTION (provided by applicant): Virtually every neural circuit that generates complex behaviors is a multitasking network: it generates not one but multiple behaviors. The fundamental question that we are addressing in this proposal is what endows a single network (central pattern generator; CPG) with this ability to generate multiple behaviors and to switch between them. We propose to study this problem in the context of three forms of feeding behavior, biting, swallowing, and egestion, in the model system Aplysia. Each of these behaviors is initiated by distinct higher-order neurons that contain different complements of neuropeptides. Using a combination of electrophysiological, biochemical, and molecular techniques we propose to test a series of hypotheses. First, we will test the hypothesis that each of the higher-order neurons elicits a distinct behavior by activating individual interneurons from the same network to a different degree. It follows that the individual interneurons, which form the CPG, must differ from each other in the functional roles they fulfill. We propose a scheme to analyze the role that individual interneurons play in generating different behaviors. We propose to test the hypothesis that differences in these roles stem from the neurons' use of different small-molecule transmitters that exert both fast and slow actions. Finally, we propose to test the hypothesis that a combination of interneuronal firing patterns, plasticity of their synaptic connections, and characteristics of the transmitters they utilize serves to counteract the maladaptive aspects that memory of previous behavior may exert when a new behavior needs to be elicited. Maladaptively persistent forms of memory of previous experiences may underlie such serious behavioral pathologies as the compulsive-obsessive disorders and depression.