New approaches for studying active neural ensembles in the nucleus accumbens

研究伏隔核中活跃神经元的新方法

基本信息

批准号：
9262277
负责人：
RALPH J DILEONE
金额：
$ 22.05万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2018-10-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Modern neuroscience studies have incorporated direct manipulations of neurons in animal models. This has recently been advanced via expression of synthetic molecules to allow for control of activity with light (e.g. optogenetics) o non- endogenous ligands (e.g. DREADDS). These approaches have revolutionized the field and are now been used more broadly. However, the power of these strategies is limited by our ability to direct them to the proper neurons. To date, the vast majority of optogenetic experiments, for example, have relied on targeting sets of neurons based on expression of a specific gene product. This results in experimental manipulations that do not reflect the normal processes in the brain, where neurons rarely fire according to these molecular categories. Recent work has leveraged molecular tools that allow for the "capture" or labeling of active neurons during behavior. These neurons, sometimes called an ensemble, can then be replayed, or inhibited, during behavior. We propose the nucleus accumbens medium spiny neurons as an excellent context to test and use this strategy. Specifically, we aim to label sets of nucleus accumbens neurons during both appetitive and aversive behavior. Preliminary data suggests that replay of these neurons is sufficient to alter future behavior - that is, we have captured an ensemble that contains positive or negative valance information. The present experiments will also characterize the circuits that mediate the appetitive/aversive ensemble effects. These efforts will connect ensemble collection with specific cells types and neural circuits, effectively enhancing the power of this approach to understanding the neurobiological basis of behavior.

描述（由申请人提供）：现代神经科学研究已经在动物模型中纳入了对神经元的直接操作，这最近通过合成分子的表达得以推进，以允许用光（例如光遗传学）或非内源配体（例如 DREADDS）控制活性。）。这些方法已经彻底改变了这个领域，并且现在得到了更广泛的应用。然而，迄今为止，这些策略的力量受到我们将它们引导到适当神经元的能力的限制。例如，光遗传学实验依赖于基于特定基因产物表达的神经元组，这导致实验操作不能反映大脑中的正常过程，神经元很少根据这些分子类别进行放电。利用分子工具可以在行为过程中“捕获”或标记活跃的神经元，然后可以在行为过程中重放或抑制这些神经元。测试并使用它具体来说，我们的目标是在食欲和厌恶行为期间设置伏隔核神经元，初步数据表明这些神经元的重放足以改变未来的行为——也就是说，我们捕获了包含正价或负价信息的集合。目前的实验还将表征介导食欲/厌恶整体效应的回路，这些努力将有效地将整体收集与特定细胞类型和神经回路连接起来。增强这种方法理解行为的神经生物学基础的能力。