Mouse Models with Multi electrode arrays

具有多电极阵列的小鼠模型

• 批准号: 7167306
• 负责人: Miguel A. L. Nicolelis
• 金额: $ 16.53万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7167306
• 关键词: amines; antidepressants; behavior test; depression; disease /disorder model; electrodes; enzyme activity; genetic polymorphism; genetically modified animals; glycogen synthase; laboratory mouse; neural information processing; neurotransmitter transport; norepinephrine; psychological stressor; serine threonine protein kinase; serotonin

Monoamines play a major role in depression. The present proposal will examine this idea by evaluating neural responses in the various mouse models of depression and it will complement the human imagining studies by providing a functional approach for identifying brain areas and neural circuits that may participate in depressive-like behaviors. It will also complement the human morphology experiments by targeting multi-electrodes in mice to cortical layers in frontal cortex that have been shown to change in depressed patients. To better understand the role of monoamines in depression, we will use multi-electrode arrays to investigate changes in cortical and subcortical neuronal activity in genetically-modified mice that have norepinephrine (NE) and/or serotonin (5-HT) dysfunction. Recently, we have developed a method to record activity simultaneously from multiple single neurons in various brain areas of freely-behaving mice. With this approach, cortical and subcortical neuronal activity will be monitored in several mouse models of depression and under different behavioral and treatment conditions. Briefly, we will study vesicular monoamine transporter 2 (VMAT2) heterozygotes, glycogen synthase kinase 3b (GSK) heterozygotes, and mice carrying a polymorphism in the Tph2 gene that has been identified in depressed patients. Wild type (WT) and mutant mice will be implanted with multi-electrode arrays targeted to the dorsomediofrontal and orbitofrontal cortices, nucleus accumbens (NAc), and central and basolateral amygdala (AMY) - the same sites that imagining studies have shown to be affected in human depressed patients. Multiple electrodes will be targeted to each of these areas simultaneously and neural activity will be assessed in freely-behaving mice under baseline conditions, after exposure to chronic stress, and following treatment with anti-depressants. In addition, as many depressed patients show disturbances in wake-sleep cycles, we will also analyze brain state dynamics throughout the cycle in mice under baseline, stress, and treatment conditions. The experiments we propose will allow for the first time the integration of molecular, cellular, systems, and behavioral data within the same animal and this approach should lead to a more complete understanding of the mechanisms underlying depression.

单胺在抑郁症中起着重要作用。目前的建议将 通过评估抑郁症小鼠模型中的神经反应来检查这个想法，它将 通过提供识别大脑区域和的功能方法来补充人类想象的研究 可能参与抑郁症行为的神经回路。它也将补充人类 形态实验通过将小鼠的多电极靶向具有额叶皮质的皮质层 被证明会在抑郁症患者中发生变化。为了更好地了解单胺在抑郁症中的作用， 我们将使用多电极阵列研究皮质和皮质下神经元活性的变化 具有去甲肾上腺素（NE）和/或5-羟色胺（5-HT）功能障碍的遗传改性小鼠。最近，我们 已经开发了一种方法来记录各种大脑中多个单个神经元的活动 自由行为的小鼠区域。使用这种方法，将监测皮质和皮质下神经元活性 在几种抑郁症的小鼠模型中，在不同的行为和治疗条件下。简而言之，我们将研究囊泡单胺转运蛋白2（VMAT2）杂合子，糖原 合酶激酶3B（GSK）杂合子和携带多态性的小鼠在TPH2基因中一直是 在抑郁症患者中确定。野生型（WT）和突变小鼠将用多电极植入 针对背侧和眶额皮质，伏隔核（NAC）和中央的阵列 和基底外侧杏仁核（AMY） - 想象研究在 人类抑郁症患者。多个电极将同时针对这些区域，并且 暴露于慢性后，将在基线条件下在基线条件下自由行为的小鼠评估神经活动 压力，并在用抗抑郁药治疗后。另外，正如许多抑郁症患者所表明的 在唤醒步骤周期中的干扰，我们还将在小鼠的整个周期中分析脑状态动力学 在基线，压力和治疗条件下。我们提出的实验将首次允许 在同一动物中的​​分子，细胞，系统和行为数据的整合以及这种方法 应该使人们对抑郁症的机制有更完整的了解。