Villers Agnès, Giese Karl Peter, Ris Laurence
Department of Neuroscience, Research Institute for Biosciences, University of Mons, B-7000 Mons, Belgium.
MRC Centre for Neurodegeneration, Institute of Psychiatry, King's College London, SE5 9NU, London, United Kingdom.
Learn Mem. 2014 Oct 16;21(11):616-26. doi: 10.1101/lm.035972.114. Print 2014 Nov.
α-calcium/calmodulin-dependent protein kinase (αCaMKII) T286-autophosphorylation provides a short-term molecular memory that was thought to be required for LTP and for learning and memory. However, it has been shown that learning can occur in αCaMKII-T286A mutant mice after a massed training protocol. This raises the question of whether there might be a form of LTP in these mice that can occur without T286 autophosphorylation. In this study, we confirmed that in CA1 pyramidal cells, LTP induced in acute hippocampal slices, after a recovery period in an interface chamber, is strictly dependent on postsynaptic αCaMKII autophosphorylation. However, we demonstrated that αCaMKII-autophosphorylation-independent plasticity can occur in the hippocampus but at the expense of synaptic specificity. This nonspecific LTP was observed in mutant and wild-type mice after a recovery period in a submersion chamber and was independent of NMDA receptors. Moreover, when slices prepared from mutant mice were preincubated during 2 h with rapamycin, high-frequency trains induced a synapse-specific LTP which was added to the nonspecific LTP. This specific LTP was related to an increase in the duration and the amplitude of NMDA receptor-mediated response induced by rapamycin.
α-钙/钙调蛋白依赖性蛋白激酶（αCaMKII）的T286自磷酸化提供了一种短期分子记忆，人们认为它是长时程增强（LTP）以及学习和记忆所必需的。然而，已有研究表明，在进行集中训练方案后，αCaMKII-T286A突变小鼠仍能发生学习。这就提出了一个问题，即在这些小鼠中是否可能存在一种无需T286自磷酸化就能发生的LTP形式。在本研究中，我们证实，在急性海马脑片中，在界面室中经过恢复期后诱导的LTP，在CA1锥体细胞中严格依赖于突触后αCaMKII自磷酸化。然而，我们证明，不依赖于αCaMKII自磷酸化的可塑性可在海马中发生，但要以突触特异性为代价。在浸没室中经过恢复期后，在突变型和野生型小鼠中均观察到这种非特异性LTP，且其不依赖于NMDA受体。此外，当将突变小鼠制备的脑片与雷帕霉素预孵育2小时后，高频刺激序列可诱导出一种突触特异性LTP，它可叠加在非特异性LTP之上。这种特异性LTP与雷帕霉素诱导的NMDA受体介导反应的持续时间和幅度增加有关。
