Voronin Leon L, Cherubini Enrico
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova str. 5a, 117485 Moscow, Russia.
J Physiol. 2004 May 15;557(Pt 1):3-12. doi: 10.1113/jphysiol.2003.058966. Epub 2004 Mar 19.
Mechanisms of long-term potentiation (LTP) maintenance are discussed in the light of the phenomenon of silent synapses. Evidence that LTP is associated with the insertion of new AMPA receptors (AMPARs) in postsynaptically silent (deaf) synapses expressing only NMDA receptors (NMDARs) before LTP induction has led to the assumption that the debate on pre- versus postsynaptic locus of LTP expression has been resolved in favour of the latter. However, recent data indicate that these synapses are mainly presynaptically silent (mute or whispering), because the probability of glutamate release (P(r)) or glutamate concentration in the cleft is too low to activate AMPARs. In this case LTP could be explained by an increase in P(r) or enhanced glutamate concentration to activate low affinity AMPARs. Optical methods to probe calcium transients in dendritic spines have revealed an increase in P(r) during LTP with concomitant postsynaptic modifications. A hypothesis is considered that accounts for the differences in both the initial failure rates between AMPAR- and NMDAR-mediated responses, and the LTP-associated decrease in failures of AMPAR-mediated responses. According to this hypothesis, glutamate release is potentiated by the strong postsynaptic depolarization used to identify NMDAR-mediated responses. We suggest that the expression of LTP may depend on coordinated pre- and postsynaptic modifications whose relative contributions vary according to the initial state of the synapse, the experimental protocol and time after induction.
基于沉默突触现象，对长时程增强（LTP）维持机制进行了讨论。有证据表明，LTP与在LTP诱导前仅表达NMDA受体（NMDARs）的突触后沉默（失聪）突触中插入新的AMPA受体（AMPARs）有关，这导致人们认为关于LTP表达的突触前与突触后位点的争论已得到解决，支持后者。然而，最近的数据表明，这些突触主要是突触前沉默（静音或低语），因为谷氨酸释放概率（P(r)）或突触间隙中的谷氨酸浓度过低，无法激活AMPARs。在这种情况下，LTP可以用P(r)增加或谷氨酸浓度增强来激活低亲和力AMPARs来解释。探测树突棘中钙瞬变的光学方法显示，LTP期间P(r)增加，并伴有突触后修饰。考虑了一个假说，该假说解释了AMPAR介导反应和NMDAR介导反应之间初始失败率的差异，以及LTP相关的AMPAR介导反应失败率的降低。根据这一假说，用于识别NMDAR介导反应的强烈突触后去极化增强了谷氨酸释放。我们认为，LTP的表达可能取决于突触前和突触后修饰的协同作用，其相对贡献根据突触的初始状态、实验方案和诱导后的时间而有所不同。
