Synaptic generation of an intracellular retrograde signal requires activation of the tyrosine kinase and mitogen-activated protein kinase signaling cascades in Aplysia.
Synaptic generation of an intracellular retrograde signal requires activation of the tyrosine kinase and mitogen-activated protein kinase signaling cascades in Aplysia.
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DOI：
10.1016/j.nlm.2015.07.017
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发表时间：
2015-11
影响因子：
2.7
通讯作者：
Carew TJ
中科院分区：
文献类型：
--
作者：
Stough S;Kopec AM;Carew TJ
记忆形成背后的细胞变化可以在特定突触处以活动依赖性方式产生。因此，一个重要的问题涉及突触信号与细胞体通信以介导这些细胞变化的机制。海兔的敏化增强的单突触回路非常适合研究这个问题，因为三个不同的亚细胞区室：（i）感觉运动 SN-MN 突触，（ii）SN 通过轴突连接投射到 MN，（iii）SN 细胞体，都可以独立操作和研究。在这里，我们报告说，在整个 SN-MN 回路或仅在突触室中的活动依赖（AD）训练，以时间和空间特定的模式激活 MAPK。具体来说，我们发现（i）训练期间，MAPK首先在SN-MN突触处短暂激活，（ii）训练后，MAPK立即在SN-MN轴突连接中短暂激活，并在SN细胞体中持续激活，最后，（iii）训练后1小时，MAPK在SN细胞体和SN-MN突触中激活。这些数据表明，突触处产生细胞内传输的逆行信号，该信号随后导致 SN 体细胞的 MAPK 激活延迟。最后，我们发现这种逆行信号需要酪氨酸激酶 (TK) 和 MEK 信号级联的激活，特别是在突触处。
Cellular changes underlying memory formation can be generated in an activity-dependent manner at specific synapses. Thus an important question concerns the mechanisms by which synaptic signals communicate with the cell body to mediate these cellular changes. A monosynaptic circuit that is enhanced by sensitization in Aplysia is well-suited to study this question because three different subcellular compartments: (i) the sensorimotor SN-MN synapses, (ii) the SN projections to MNs via axonal connections, (iii) the SN cell bodies, can all be manipulated and studied independently. Here, we report that activity-dependent (AD) training in either the entire SN-MN circuit or in only the synaptic compartment, activates MAPK in a temporally and spatially specific pattern. Specifically, we find (i) MAPK activation is first transiently generated at SN-MN synapses during training, (ii) immediately after training MAPK is transiently activated in SN-MN axonal connections and persistently activated in SN cell bodies, and finally, (iii) MAPK is activated in SN cell bodies and SN-MN synapses 1hr after training. These data suggest that there is an intracellularly transported retrograde signal generated at the synapse which is later responsible for delayed MAPK activation at SN somata. Finally, we find that this retrograde signal requires activation of tyrosine kinase (TK) and MEK signaling cascades specifically at the synapses.