Synaptic Microcircuits Underlying Associative Learning

动物学会将中性的感官线索与积极或消极的偶然事件联系起来， 来做出适应性决策。灵活更新这些已获取的关联， 意外变化也很重要。未能更新内部表征在某些情况下起着因果作用。 精神障碍，包括精神分裂症和焦虑症。虽然获取和更新的神经基质 虽然已经在哺乳动物模型中研究了这种关联，但哺乳动物大脑的复杂性使其 很难获得精确的细胞和突触机制的理解。果蝇表现出灵活的 联想学习：他们学会避免与电击配对的气味，并熄灭学到的气味。 当气味随后出现而没有休克时，苍蝇有强大的遗传工具， 在蘑菇体脑区域中用细胞分辨率操纵和可视化神经活动 (MB)学习过程中神经可塑性的发生。我们的长期目标是利用果蝇 对MB的突触微电路如何实现获取和消退的机械见解。 我们的新假设是，多巴胺神经元的可塑性嵌入在一个经常性的突触微电路 存在于蝇蕈状体中是气味休克关联消失的基础。为了验证这一假设， 利用体内Ca2+成像和光遗传学来可视化和操纵神经活动的动态变化 特定的遗传靶向MB细胞类型作为一个苍蝇获得和传播之间的联系， 气味和令人厌恶的电击

Animals learn to associate otherwise neutral sensory cues with positive or negative contingencies and rely on those associations to make adaptive decisions. Flexible updating of these acquired associations as contingencies change is also important. Failure to update internal representations plays a causal role in some mental disorders, including schizophrenia and anxiety. While the neural substrates of acquiring and updating associations have been studied in mammalian models, the complexity of the mammalian brain has made it difficult to obtain precise cellular and synaptic mechanistic understanding. Drosophila flies exhibit flexible associative learning: they learn to avoid an odor paired with electric shock, and extinguish that learned association when the odor is later presented without shock. Flies have powerful genetic tools to allow precise manipulation and visualization of neural activity with cellular resolution in the mushroom body brain region (MB), where neural plasticity underlying learning occurs. Our long-term goal is to use Drosophila to gain mechanistic insight into how acquisition and extinction are implemented by synaptic microcircuits of the MB. Our novel hypothesis is that plasticity of dopamine neurons embedded in a recurrent synaptic microcircuit residing in the fly mushroom body underlies extinction of odor-shock associations. To test this hypothesis we employ in vivo Ca2+ imaging and optogenetics to visualize and manipulate dynamic changes in neural activity of specific genetically targeted MB cell types as a fly acquires and extinguishes an association between a neutral odor and aversive electric shock.