Tomosyn-dependent regulation of synaptic transmission is required for a late phase of associative odor memory
Tomosyn-dependent regulation of synaptic transmission is required for a late phase of associative odor memory
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DOI：
10.1073/pnas.1110184108
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发表时间：
2011-11-08
影响因子：
11.1
通讯作者：
Richmond, Janet E.
中科院分区：
文献类型：
--
作者：
Chen, Kaiyun;Richlitzki, Antje;Richmond, Janet E.
突触囊泡分泌需要融合SNARE复合物的组装。因此，调节SNARE复合物形成的蛋白质可以显著影响突触强度。SNARE结合蛋白tomosyn已显示通过在非融合复合物中螯合SNARE蛋白而有效抑制胞吐作用。Tomosyn-SNARE相互作用受蛋白激酶A（PKA）调节，PKA是一种与学习和记忆有关的酶，表明Tomosyn可能是PKA依赖性突触可塑性的重要效应子。我们在果蝇中测试了这一假设，其中PKA通路在联想学习中的作用已经得到了很好的证实。我们首先确定，panneuronal tomosyn敲低RNAi增强突触强度在果蝇幼虫神经肌肉接头，通过增加诱发反应的持续时间。接下来，我们在厌恶性嗅觉学习后3分钟（早期记忆）和3小时（晚期记忆）测定记忆表现。尽管早期记忆不受tomosyn敲低的影响，但晚期记忆减少了50%。晚期记忆是由稳定和不稳定的成分组成的。进一步的分析确定，tomosyn是麻醉敏感的不稳定成分所特别需要的，此前已证明该成分需要通过蘑菇体内的PKA进行cAMP信号传导。总之，这些数据表明，tomosyn在突触传递的调节中具有保守的作用，并提供了行为证据，tomosyn参与晚期联想记忆的特定组成部分。
Synaptic vesicle secretion requires the assembly of fusogenic SNARE complexes. Consequently proteins that regulate SNARE complex formation can significantly impact synaptic strength. The SNARE binding protein tomosyn has been shown to potently inhibit exocytosis by sequestering SNARE proteins in nonfusogenic complexes. The tomosyn-SNARE interaction is regulated by protein kinase A (PKA), an enzyme implicated in learning and memory, suggesting tomosyn could be an important effector in PKA-dependent synaptic plasticity. We tested this hypothesis in Drosophila, in which the role of the PKA pathway in associative learning has been well established. We first determined that panneuronal tomosyn knockdown by RNAi enhanced synaptic strength at the Drosophila larval neuromuscular junction, by increasing the evoked response duration. We next assayed memory performance 3 min (early memory) and 3 h (late memory) after aversive olfactory learning. Whereas early memory was unaffected by tomosyn knockdown, late memory was reduced by 50%. Late memory is a composite of stable and labile components. Further analysis determined that tomosyn was specifically required for the anesthesia-sensitive, labile component, previously shown to require cAMP signaling via PKA in mushroom bodies. Together these data indicate that tomosyn has a conserved role in the regulation of synaptic transmission and provide behavioral evidence that tomosyn is involved in a specific component of late associative memory.