2012年10月19日 讯 /生物谷BIOON/ --近日，美国纽约大学和加州大学欧文分校的神经科学家发现了短期、中期和长期记忆形成过程中活化分子的时间和位置。这项研究发现发表在近期的PNAS上，为理解记忆形成的分子机制提供了新思路。
领导者Thomas Carew说，这项研究成果可帮助我们更好的理解记忆是如何形成的，记忆形成并不是简单的将分子开或关的过程，而是复杂的分子之间的时空作用关系。
此前，已有研究揭示与记忆形成的分子信号途径，但分子之间的空间关系及在这个过程中它们何时激活尚不清楚。
为了解答这个问题，研究者对加利福尼亚海参（sea slug）的神经元进行了研究，由于海参的神经元比其他高等生物如脊椎动物长10到50倍，且拥有一个较小的神经网络，有助于检测到记忆形成过程中的分子信号，因此是此类研究的理想选择。此外，记忆形成机制在进化上非常保守，海参的记忆形成也与哺乳动物类似，这样就有助了解人的记忆是如何形成的。
研究人员将目标锁定在两种分子--MAPK和PKA，因为已知二者与多种形式的记忆和突触可塑性（synaptic plasticity）有关。首先，研究者将海参进行敏化培训（sensitization training），即通过对尾巴处的神经进行温和的刺激诱导增强的行为反射响应（behavioral reflex responsiveness），然后检测MAPK和PKA的分子活性。这两个分子之间的相互作用尚不清楚。
结果发现，在记忆形成过程中MAPK和PKA的活性是时空变化的，在中期记忆如几个小时和长期记忆如几天，MAPK和PKA都激活。而少于30分钟的短期记忆仅PKA激活。（生物谷Bioon.com）
doi:10.1073/pnas.1209956109
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Local synaptic integration of mitogen-activated protein kinase and protein kinase A signaling mediates intermediate-term synaptic facilitation in Aplysia
Xiaojing Yea, Andreea Marinab, and Thomas J. Carewa,
It is widely appreciated that memory processing engages a wide range of molecular signaling cascades in neurons, but how these cascades are temporally and spatially integrated is not well understood. To explore this important question, we used Aplysia californica as a model system. We simultaneously examined the timing and subcellular location of two signaling molecules, MAPK (ERK1/2) and protein kinase A (PKA), both of which are critical for the formation of enduring memory for sensitization. We also explored their interaction during the formation of enduring synaptic facilitation, a cellular correlate of memory, at tail sensory-to-motor neuron synapses. We find that repeated tail nerve shock (TNS, an analog of sensitizing training) immediately and persistently activates MAPK in both sensory neuron somata and synaptic neuropil. In contrast, we observe immediate PKA activation only in the synaptic neuropil. It is followed by PKA activation in both compartments 1 h after TNS. Interestingly, blocking MAPK activation during, but not after, TNS impairs PKA activation in synaptic neuropil without affecting the delayed PKA activation in sensory neuron somata. Finally, by applying inhibitors restricted to the synaptic compartment, we show that synaptic MAPK activation during TNS is required for the induction of intermediate-term synaptic facilitation, which leads to the persistent synaptic PKA activation required to maintain this facilitation. Collectively, our results elucidate how MAPK and PKA signaling cascades are spatiotemporally integrated in a single neuron to support synaptic plasticity underlying memory formation.
