2012年10月19日 訊 /生物谷BIOON/ --近日,，美國紐約大學和加州大學歐文分校的神經(jīng)科學家發(fā)現(xiàn)了短期,、中期和長期記憶形成過程中活化分子的時間和位置,。這項研究發(fā)現(xiàn)發(fā)表在近期的PNAS上,，為理解記憶形成的分子機制提供了新思路,。
領(lǐng)導者Thomas Carew說,，這項研究成果可幫助我們更好的理解記憶是如何形成的,，記憶形成并不是簡單的將分子開或關(guān)的過程,，而是復雜的分子之間的時空作用關(guān)系。
此前,，已有研究揭示與記憶形成的分子信號途徑,，但分子之間的空間關(guān)系及在這個過程中它們何時激活尚不清楚。
為了解答這個問題,，研究者對加利福尼亞海參（sea slug）的神經(jīng)元進行了研究,，由于海參的神經(jīng)元比其他高等生物如脊椎動物長10到50倍，且擁有一個較小的神經(jīng)網(wǎng)絡(luò),，有助于檢測到記憶形成過程中的分子信號,，因此是此類研究的理想選擇。此外,，記憶形成機制在進化上非常保守,，海參的記憶形成也與哺乳動物類似，這樣就有助了解人的記憶是如何形成的,。
研究人員將目標鎖定在兩種分子--MAPK和PKA,，因為已知二者與多種形式的記憶和突觸可塑性（synaptic plasticity）有關(guān),。首先，研究者將海參進行敏化培訓（sensitization training）,，即通過對尾巴處的神經(jīng)進行溫和的刺激誘導增強的行為反射響應(yīng)（behavioral reflex responsiveness）,，然后檢測MAPK和PKA的分子活性。這兩個分子之間的相互作用尚不清楚,。
結(jié)果發(fā)現(xiàn),，在記憶形成過程中MAPK和PKA的活性是時空變化的，在中期記憶如幾個小時和長期記憶如幾天,，MAPK和PKA都激活,。而少于30分鐘的短期記憶僅PKA激活。（生物谷Bioon.com）
doi:10.1073/pnas.1209956109
PMC:
PMID:
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.
