New approaches for studying active neural ensembles in the nucleus accumbens

 描述（由申请人提供）：现代神经科学研究已纳入动物模型中神经元的直接操作。这最近已经通过合成分子的表达得到了进展，以允许用光（例如光遗传学）或非内源性配体（例如DREADDS）控制活性。这些方法已经彻底改变了该领域，现在被更广泛地使用。然而，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，迄今为止，绝大多数光遗传学实验都依赖于基于特定基因产物表达的靶向神经元组。这导致实验操作无法反映大脑的正常过程，大脑中的神经元很少根据这些分子类别激发。最近的工作利用了分子工具，允许在行为过程中“捕获”或标记活跃的神经元。这些神经元，有时被称为集合，然后可以在行为过程中重放或抑制。我们提出了一个很好的背景下，以测试和使用这种策略的神经核中多刺神经元。具体来说，我们的目标是在食欲和厌恶行为期间标记丘脑核神经元。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，我们已经捕获了一个包含正或负价信息的整体。本实验还将表征介导食欲/厌恶合奏效果的电路。这些努力将有效地将集合收集与特定细胞类型和神经回路联系起来， 增强这种方法理解行为的神经生物学基础的能力。

 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.