Norepinephrine modulation of neocortex during flexible behavior

摘要 去甲肾上腺素是一种神经递质，被认为与驱动行为灵活性有关。它是由一个 新皮质内有少量神经元。然而，人们对这些神经元的信号却知之甚少。 提供，以及新皮质中的目标如何使用这些信号，在 哺乳动物。这项建议旨在确定该基因座中去甲肾上腺素释放神经元的功能 蓝斑，前脑去甲肾上腺素的主要来源。要研究的行为涉及不同的类型 灵活性：能够在使用不同的感觉模式之间切换，以选择相关的感觉模式 获得奖励，并有能力在不同的选择中进行选择，这些选择会随着变化而产生奖励 概率。该项目的目标是将已识别的去甲肾上腺素释放神经元的动作电位联系起来。 对初级躯体感觉皮层膜电位、动作电位和钙动力学的影响 前额叶皮质，在灵活行为的背景下。 三个目标检验了三个假设，这三个假设解决了关于基因功能的不同机械问题 去甲肾上腺素在新皮质中的作用：1)去甲肾上腺素作用于感觉皮质，以调节 感觉刺激；2)去甲肾上腺素调节相关感觉模式之间的切换；3) 去甲肾上腺素和前额叶皮质活动与行为的动态更新相关。同时进行 控制良好时大脑皮层去甲肾上腺素神经元及其靶点活性的测定 在老鼠身上的行为任务，将使测试这三个假说成为可能。归根结底，理解何时和 大脑中释放去甲肾上腺素的地方对于理解灵活的行为是必要的，而且 依赖去甲肾上腺素信号的注意力和情绪障碍。

SUMMARY Norepinephrine is a neurotransmitter thought to be involved in driving behavioral flexibility. It is released by a small number of neurons throughout the neocortex. Little is known, however, about what signals these neurons provide, and how targets in neocortex use those signals, in the context of well-controlled behaviors in mammals. This proposal aims to determine functions of norepinephrine-releasing neurons in the locus coeruleus, the primary source of forebrain norepinephrine. The behaviors to be studied involve different types of flexibility: the ability to switch between using different sensory modalities to select the relevant one for receiving a reward, and the ability to choose among different alternatives that yield reward with changing probabilities. The goal of the project is to link action potentials from identified norepinephrine-releasing neurons to membrane potential, action potentials, and calcium dynamics, in primary somatosensory cortex and prefrontal cortex, in the context of flexible behavior. Three aims test three hypotheses that address different mechanistic questions about the functions of norepinephrine in neocortex: 1) norepinephrine acts in sensory cortex to modulate the perceptual outcome of a sensory stimulus; 2) norepinephrine regulates switching between relevant sensory modalities; 3) norepinephrine and prefrontal cortex activity correlate with dynamic updating of behavior. Simultaneous measurements of activity of norepinephrine neurons and their targets in neocortex, during well-controlled behavioral tasks in mice, will enable testing these three hypotheses. Ultimately, understanding when and where norepinephrine is released in the brain will be necessary to understand flexible behavior in general, and disorders of attention and mood that rely on norepinephrine signaling.