Young Jennie Z, Nguyen Peter V
Laboratory of Synaptic Plasticity, University of Alberta School of Medicine, Edmonton, Alberta, T6G 2H7, Canada.
J Neurosci. 2005 Aug 3;25(31):7221-31. doi: 10.1523/JNEUROSCI.0909-05.2005.
Long-term potentiation (LTP) is an enhancement of synaptic strength that may contribute to information storage in the mammalian brain. LTP expression can be regulated by previous synaptic activity, a process known as "metaplasticity." Cell-wide occurrence of metaplasticity may regulate synaptic strength. However, few reports have demonstrated metaplasticity at synapses that are silent during activity at converging synaptic inputs. We describe a novel form of cell-wide metaplasticity in hippocampal area CA1. Low-frequency stimulation (LFS) decreased the stability of long-lasting LTP ["late" LTP (L-LTP)] induced later at the same inputs (homosynaptic inhibition) and at other inputs converging on the same postsynaptic cells (heterosynaptic inhibition). Significantly, heterosynaptic inhibition of L-LTP also occurred across basal and apical dendrites ("heterodendritic" inhibition). Because transient early LTP (E-LTP) was not affected by previous LFS, we examined the effects of LFS on the consolidation of E-LTP to L-LTP. The duration of E-LTP induced at one set of inputs can be extended by capturing L-LTP-associated gene products generated by previous activity at other inputs to the same postsynaptic neurons. LFS applied homosynaptically or heterosynaptically before L-LTP induction did not impair synaptic capture by subsequent E-LTP stimulation, suggesting that LFS does not impair L-LTP-associated transcription. In contrast, LFS applied just before E-LTP (homosynaptically or heterosynaptically) prevented synaptic tagging, and capture of L-LTP expression. Thus, LFS inhibits synaptic tagging to impair expression of subsequent L-LTP. Such anterograde inhibition represents a novel way in which synaptic activity can regulate the expression of future long-lasting synaptic plasticity in a cell-wide manner.
长时程增强（LTP）是突触强度的增强，可能有助于哺乳动物大脑中的信息存储。LTP的表达可由先前的突触活动调节，这一过程称为“元可塑性”。元可塑性在全细胞水平上的发生可能会调节突触强度。然而，很少有报告证明在汇聚突触输入活动期间沉默的突触处存在元可塑性。我们描述了海马CA1区一种新型的全细胞元可塑性形式。低频刺激（LFS）降低了随后在相同输入处（同突触抑制）以及汇聚于同一突触后细胞的其他输入处（异突触抑制）诱导产生的持久LTP[“晚期”LTP（L-LTP）]的稳定性。值得注意的是，L-LTP的异突触抑制也发生在基底和顶端树突之间（“异树突”抑制）。由于短暂的早期LTP（E-LTP）不受先前LFS的影响，我们研究了LFS对E-LTP向L-LTP巩固的影响。在一组输入处诱导产生的E-LTP的持续时间可以通过捕获由同一突触后神经元其他输入处先前活动产生的与L-LTP相关的基因产物而延长。在L-LTP诱导之前进行同突触或异突触施加的LFS不会损害随后E-LTP刺激的突触捕获，这表明LFS不会损害与L-LTP相关的转录。相反，就在E-LTP之前（同突触或异突触）施加的LFS会阻止突触标记以及L-LTP表达的捕获。因此，LFS抑制突触标记以损害随后L-LTP的表达。这种顺行性抑制代表了一种新的方式，通过这种方式突触活动可以在全细胞水平上调节未来持久突触可塑性的表达。
