Nishiyama M, Hong K, Mikoshiba K, Poo M M, Kato K
Department of Biology, University of California at San Diego, La Jolla 92093-0357, USA.
Nature. 2000 Nov 30;408(6812):584-8. doi: 10.1038/35046067.
Activity-induced synaptic modification is essential for the development and plasticity of the nervous system. Repetitive correlated activation of pre- and postsynaptic neurons can induce persistent enhancement or decrement of synaptic efficacy, commonly referred to as long-term potentiation or depression (LTP or LTD). An important unresolved issue is whether and to what extent LTP and LTD are restricted to the activated synapses. Here we show that, in the CA1 region of the hippocampus, reduction of postsynaptic calcium influx by partial blockade of NMDA (N-methyl-D-aspartate) receptors results in a conversion of LTP to LTD and a loss of input specificity normally associated with LTP, with LTD appearing at heterosynaptic inputs. The induction of LTD at homo- and heterosynaptic sites requires functional ryanodine receptors and inositol triphosphate (InsP3) receptors, respectively. Functional blockade or genetic deletion of type 1 InsP3 receptors led to a conversion of LTD to LTP and elimination of heterosynaptic LTD, whereas blocking ryanodine receptors eliminated only homosynaptic LTD. Thus, postsynaptic Ca2+, deriving from Ca2+ influx and differential release of Ca2+ from internal stores through ryanodine and InsP3 receptors, regulates both the polarity and input specificity of activity-induced synaptic modification.
活动诱导的突触修饰对于神经系统的发育和可塑性至关重要。突触前和突触后神经元的重复相关激活可诱导突触效能的持续增强或减弱，通常称为长时程增强或长时程抑制（LTP或LTD）。一个重要的未解决问题是LTP和LTD是否以及在多大程度上局限于被激活的突触。在这里，我们表明，在海马体的CA1区域，通过部分阻断NMDA（N-甲基-D-天冬氨酸）受体来减少突触后钙内流，会导致LTP转变为LTD，并丧失通常与LTP相关的输入特异性，LTD出现在异突触输入处。在同突触和异突触位点诱导LTD分别需要功能性的兰尼碱受体和三磷酸肌醇（InsP3）受体。对1型InsP3受体进行功能性阻断或基因缺失会导致LTD转变为LTP，并消除异突触LTD，而阻断兰尼碱受体只会消除同突触LTD。因此，源自钙内流以及通过兰尼碱和InsP3受体从内部储存中差异释放的钙的突触后Ca2+，调节活动诱导的突触修饰的极性和输入特异性。
