Leibniz Institute for Neurobiology, Department Genetics of Learning and Memory, 39118 Magdeburg, Germany
Leibniz Institute for Neurobiology, Department Genetics of Learning and Memory, 39118 Magdeburg, Germany.
J Neurosci. 2020 Jul 29;40(31):5990-6006. doi: 10.1523/JNEUROSCI.0290-20.2020. Epub 2020 Jun 25.
An adaptive transition from exploring the environment in search of vital resources to exploiting these resources once the search was successful is important to all animals. Here we study the neuronal circuitry that allows larval of either sex to negotiate this exploration-exploitation transition. We do so by combining Pavlovian conditioning with high-resolution behavioral tracking, optogenetic manipulation of individually identified neurons, and EM data-based analyses of synaptic organization. We find that optogenetic activation of the dopaminergic neuron DAN-i1 can both establish memory during training and acutely terminate learned search behavior in a subsequent recall test. Its activation leaves innate behavior unaffected, however. Specifically, DAN-i1 activation can establish associative memories of opposite valence after paired and unpaired training with odor, and its activation during the recall test can terminate the search behavior resulting from either of these memories. Our results further suggest that in its behavioral significance DAN-i1 activation resembles, but does not equal, sugar reward. Dendrogram analyses of all the synaptic connections between DAN-i1 and its two main targets, the Kenyon cells and the mushroom body output neuron MBON-i1, further suggest that the DAN-i1 signals during training and during the recall test could be delivered to the Kenyon cells and to MBON-i1, respectively, within previously unrecognized, locally confined branching structures. This would provide an elegant circuit motif to terminate search on its successful completion. In the struggle for survival, animals have to explore their environment in search of food. Once food is found, however, it is adaptive to prioritize exploiting it over continuing a search that would now be as pointless as searching for the glasses you are wearing. This exploration-exploitation trade-off is important for animals and humans, as well as for technical search devices. We investigate which of the only 10,000 neurons of a fruit fly larva can tip the balance in this trade-off, and identify a single dopamine neuron called DAN-i1 that can do so. Given the similarities in dopamine neuron function across the animal kingdom, this may reflect a general principle of how search is terminated once it is successful.
从探索环境以寻找重要资源到成功搜索后利用这些资源的自适应转变对所有动物都很重要。在这里，我们研究了允许幼虫无论性别都能进行这种探索-利用转变的神经元回路。我们通过将巴甫洛夫条件反射与高分辨率行为跟踪、单独识别神经元的光遗传学操作以及基于 EM 数据的突触组织分析相结合来实现这一点。我们发现，多巴胺能神经元 DAN-i1 的光遗传学激活既可以在训练过程中建立记忆，又可以在随后的回忆测试中急性终止已习得的搜索行为。然而，其激活不会影响先天行为。具体来说，DAN-i1 的激活可以在与气味进行配对和非配对训练后建立相反效价的联想记忆，并且其在回忆测试中的激活可以终止源自这些记忆中的任何一个的搜索行为。我们的结果还表明，在其行为意义上，DAN-i1 的激活类似于但不等于糖奖励。DAN-i1 与其两个主要靶标，即 Kenyon 细胞和蘑菇体输出神经元 MBON-i1 之间的所有突触连接的系统发育树分析进一步表明，DAN-i1 在训练期间和回忆测试期间的信号可以分别传递到 Kenyon 细胞和 MBON-i1，这是在以前未被识别的、局部受限的分支结构内进行的。这将提供一个优雅的电路模式，以成功完成搜索后终止搜索。在为生存而奋斗的过程中，动物必须探索环境以寻找食物。然而，一旦找到食物，优先利用它而不是继续搜索就会变得毫无意义，就像搜索你正在戴的眼镜一样。这种探索-利用权衡对动物和人类以及技术搜索设备都很重要。我们研究了果蝇幼虫的 10000 个神经元中哪一个可以在这种权衡中改变平衡，并确定了一个名为 DAN-i1 的单一多巴胺神经元可以做到这一点。鉴于多巴胺能神经元在动物王国中的功能相似，这可能反映了一旦搜索成功，搜索如何终止的一般原则。
