Salk Institute for Biological Studies, La Jolla, California 92037, USA.
J Neurosci. 2013 Jan 23;33(4):1314-25. doi: 10.1523/JNEUROSCI.3219-12.2013.
Synapses onto distal dendritic tufts are believed to function by modulating time-locked proximal inputs; however, the role of these synapses when proximal inputs are asynchronous or silent is unknown. Surprisingly, we found that activation of apical tuft synapses alone resulted in heterosynaptic potentiation of proximal synapses. In mouse adult hippocampal CA1 pyramidal neurons, we show that activation of distal inputs from the entorhinal cortex (EC) specifically strengthens proximal synapses projecting from CA3. This slow AMPA receptor-mediated potentiation is accompanied by increased synaptic GluN2B-containing NMDA receptors, which are normally restricted to juvenile animals. These two synaptic modifications interact to generate striking bidirectional metaplastic changes. Heterosynaptically potentiated synapses become resistant to subsequent long-term potentiation (LTP) as the two forms of AMPA receptor-mediated potentiation occlude. However, this is only true when the LTP induction protocol is relatively weak. When it is strong and repeated, the magnitude of LTP after heterosynaptic plasticity is greatly increased, specifically through the activation of GluN2B-containing NMDA receptors. Thus, CA1 neurons expressing heterosynaptic potentiation induced by external sensory input from the EC become more strongly driven by internally generated environmental representations from CA3. Furthermore, subsequent SC LTP in this ensemble is shifted to potentiate only strongly activated CA3 inputs, while endowing these synapses with enhanced potentiation. These results show that one set of inputs can exert long-lasting heterosynaptic control over another, allowing the coupling of two functionally and spatially distinct pathways, thereby greatly expanding the repertoire of cellular and network plasticity.
树突远端末梢上的突触被认为通过调节时间锁定的近端输入起作用；然而，当近端输入不同步或沉默时，这些突触的作用尚不清楚。令人惊讶的是，我们发现仅激活树突棘突触就能导致近端突触的异突触增强。在成年小鼠海马 CA1 锥体神经元中，我们发现来自内嗅皮层（EC）的远端输入的激活特异性增强了从 CA3 投射的近端突触。这种缓慢的 AMPA 受体介导的增强伴随着突触 GluN2B 含量增加的 NMDA 受体，这些受体通常局限于幼年动物。这两种突触修饰相互作用产生了显著的双向代谢变化。异突触增强的突触对随后的长时程增强（LTP）变得不敏感，因为两种形式的 AMPA 受体介导的增强会相互排斥。然而，只有当 LTP 诱导方案相对较弱时才是如此。当它很强且重复时，异突触可塑性后的 LTP 幅度大大增加，特别是通过激活含有 GluN2B 的 NMDA 受体。因此，表达由 EC 外部感觉输入引起的异突触增强的 CA1 神经元，由 CA3 内部产生的环境表示更强烈地驱动。此外，在这个集合中，后续的 SC LTP 被转移到仅增强强烈激活的 CA3 输入，同时赋予这些突触增强的增强。这些结果表明，一组输入可以对另一组输入施加持久的异突触控制，从而允许两个功能和空间上不同的通路耦合，从而极大地扩展了细胞和网络可塑性的范围。
