Dopaminergic modulation of cAMP drives nonlinear plasticity across the Drosophila mushroom body lobes.
Dopaminergic modulation of cAMP drives nonlinear plasticity across the Drosophila mushroom body lobes.
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DOI：
10.1016/j.cub.2014.03.021
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发表时间：
2014-04-14
期刊：
影响因子：
9.2
通讯作者：
Tomchik, Seth M.
中科院分区：
文献类型：
--
作者：
Boto, Tamara;Louis, Thierry;Jindachomthong, Kantiya;Jalink, Kees;Tomchik, Seth M.
多巴胺能神经元的活动是必要的，足以引起学习相关的可塑性的神经元网络，调节学习。在嗅觉经典条件反射过程中，大量多巴胺能神经元被激活，在广泛的突触后神经元中释放多巴胺。目前还不清楚这种弥漫性的多巴胺释放是如何产生记忆形成所需的高度局部化的可塑性模式的。在这里，我们已经绘制了多巴胺能调制的空间模式的果蝇蘑菇体（MB）神经元的细胞内信号和可塑性，结合突触前热刺激多巴胺能神经元突触后功能成像在体内。多巴胺能神经元的刺激在MB的多个空间区域产生cAMP的增加。然而，气味介绍配对刺激多巴胺能神经元诱发可塑性的钙离子反应在离散的空间模式。这些模式的可塑性与行为要求的每一组MB神经元在厌恶和食欲条件反射。最后，广泛的cAMP升高差异促进γ叶的反应，这表明它是更敏感的cAMP的升高，它首先被招募到多巴胺依赖的记忆痕迹。这些数据表明，学习相关的可塑性的空间模式依赖于突触后神经元对cAMP信号的敏感性。这可能代表了一种机制，通过这种机制，单周期条件反射将短期记忆分配给特定的合格神经元子集（伽马神经元）。
Activity of dopaminergic neurons is necessary and sufficient to evoke learning-related plasticity in neuronal networks that modulate learning. During olfactory classical conditioning, large subsets of dopaminergic neurons are activated, releasing dopamine across broad sets of postsynaptic neurons. It is unclear how such diffuse dopamine release generates the highly localized patterns of plasticity required for memory formation. Here we have mapped spatial patterns of dopaminergic modulation of intracellular signaling and plasticity in Drosophila mushroom body (MB) neurons, combining presynaptic thermogenetic stimulation of dopaminergic neurons with postsynaptic functional imaging in vivo. Stimulation of dopaminergic neurons generated increases in cAMP across multiple spatial regions in the MB. However, odor presentation paired with stimulation of dopaminergic neurons evoked plasticity in Ca2+ responses in discrete spatial patterns. These patterns of plasticity correlated with behavioral requirements for each set of MB neurons in aversive and appetitive conditioning. Finally, broad elevation of cAMP differentially facilitated responses in the gamma lobe, suggesting that it is more sensitive to elevations of cAMP, and that it is recruited first into dopamine-dependent memory traces. These data suggest that the spatial pattern of learning-related plasticity is dependent on the postsynaptic neurons’ sensitivity to cAMP signaling. This may represent a mechanism through which single-cycle conditioning allocates short-term memory to a specific subset of eligible neurons (gamma neurons).
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