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Norepinephrine modulation of neocortex during flexible behavior

灵活行为期间去甲肾上腺素对新皮质的调节

基本信息

批准号：
10320438
负责人：
Jeremiah Yaacov Cohen
金额：
$ 81.08万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-12-15 至 2023-11-30
项目状态：
已结题

项目摘要

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.

总结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。它是由一个少量的神经元遍布整个新皮层。然而，人们对这些神经元发出的信号知之甚少，提供，以及新皮层中的目标如何使用这些信号，在良好控制的行为背景下，哺乳动物本研究的目的是确定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。所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方式之间切换，以选择相关的一个，接受奖励，以及在不同的替代方案中选择的能力，这些替代方案随着变化而产生奖励。概率该项目的目标是将已识别的释放去甲肾上腺素的神经元的动作电位联系起来膜电位，动作电位和钙动力学，在初级躯体感觉皮层，前额叶皮层，在灵活行为的背景下。三个目标测试三个假设，解决不同的机械问题的功能，新皮层中的去甲肾上腺素：1）去甲肾上腺素在感觉皮层中起作用以调节感觉刺激; 2）去甲肾上腺素调节相关感觉模态之间的切换; 3）去甲肾上腺素和前额皮质活动与行为的动态更新相关。同时测量去甲肾上腺素神经元及其在新皮层中的靶点的活性，在良好控制的过程中，小鼠的行为任务，将使测试这三个假设。最终，了解何时以及去甲肾上腺素在大脑中释放的位置对于理解一般的灵活行为是必要的，依赖去甲肾上腺素信号的注意力和情绪障碍。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Simultaneous recordings of pupil size variation and locus coeruleus activity in mice.

DOI：
10.1016/j.xpro.2023.102785
发表时间：
2024-03-15
期刊：
STAR PROTOCOLS
影响因子：
0
作者：
Megemont, Marine;Tortorelli, Lucas S.;McBurney-Lin, Jim;Cohen, Jeremiah Y.;O'Connor, Daniel H.;Yang, Hongdian
通讯作者：
Yang, Hongdian

Aversive stimuli bias corticothalamic responses to motivationally significant cues.