Laboratory of Functional Neuroscience, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, Japan.
J Physiol. 2011 Jul 15;589(Pt 14):3559-73. doi: 10.1113/jphysiol.2011.206169. Epub 2011 Jun 6.
Hippocampal early (E-) long-term potentiation (LTP) and long-term depression (LTD) elicited by a weak stimulus normally fades within 90 min. Late (L-) LTP and LTD elicited by strong stimuli continue for >180 min and require new protein synthesis to persist. If a strong tetanus is applied once to synaptic inputs, even a weak tetanus applied to another synaptic input can evoke persistent LTP. A synaptic tag is hypothesized to enable the capture of newly synthesized synaptic molecules. This process, referred to as synaptic tagging, is found between not only the same processes (i.e. E- and L-LTP; E- and L-LTD) but also between different processes (i.e. E-LTP and L-LTD; E-LTD and L-LTP) induced at two independent synaptic inputs (cross-tagging). However, the mechanisms of synaptic tag setting remain unclear. In our previous study, we found that synaptic associativity in the hippocampal Schaffer collateral pathway depended on neuropsin (kallikrein-related peptidase 8 or KLK8), a plasticity-related extracellular protease. In the present study, we investigated how neuropsin participates in synaptic tagging and cross-tagging. We report that neuropsin is involved in synaptic tagging during LTP at basal and apical dendritic inputs. Moreover, neuropsin is involved in synaptic tagging and cross-tagging during LTP at apical dendritic inputs via integrin β1 and calcium/calmodulin-dependent protein kinase II signalling. Thus, neuropsin is a candidate molecule for the LTP-specific tag setting and regulates the transformation of E- to L-LTP during both synaptic tagging and cross-tagging.
海马体早期（E-）长时程增强（LTP）和长时程抑制（LTD）由弱刺激引起，通常在 90 分钟内消失。由强刺激引起的晚期（L-）LTP 和 LTD 持续时间超过 180 分钟，需要新的蛋白质合成才能持续。如果一次对突触输入施加强强直刺激，即使对另一个突触输入施加弱强直刺激也可以引发持续的 LTP。突触标签被假设为能够捕获新合成的突触分子。这个过程被称为突触标记，不仅在相同的过程（即 E-LTP 和 L-LTP；E-LTD 和 L-LTD）之间，而且在两个独立的突触输入（交叉标记）诱导的不同过程（即 E-LTP 和 L-LTD；E-LTD 和 L-LTP）之间都存在。然而，突触标记设置的机制仍不清楚。在我们之前的研究中，我们发现海马体 Schaffer 侧枝通路中的突触关联性依赖于神经蛋白酶（激肽释放酶相关肽酶 8 或 KLK8），一种与可塑性相关的细胞外蛋白酶。在本研究中，我们研究了神经蛋白酶如何参与突触标记和交叉标记。我们报告说，神经蛋白酶参与了基底和树突棘输入的 LTP 期间的突触标记。此外，神经蛋白酶通过整合素β1 和钙/钙调蛋白依赖性蛋白激酶 II 信号通路参与树突棘输入的 LTP 期间的突触标记和交叉标记。因此，神经蛋白酶是 LTP 特异性标记设置的候选分子，并且在突触标记和交叉标记期间调节 E-LTP 向 L-LTP 的转化。
