Department Biochemistry, Microbiology and Bio-informatics, Université Laval; Axis of Cellular and Molecular Neuroscience, IUSMQ, Québec, Canada.
J Neurosci. 2014 Mar 12;34(11):3864-77. doi: 10.1523/JNEUROSCI.2253-13.2014.
Postsynaptic calcium (Ca2+) nonlinearities allow neuronal coincidence detection and site-specific plasticity. Whether such events exist in dendrites of interneurons and play a role in regulation of synaptic efficacy remains unknown. Here, we used a combination of whole-cell patch-clamp recordings and two-photon Ca2+ imaging to reveal Ca2+ nonlinearities associated with synaptic integration in dendrites of mouse hippocampal CA1 fast-spiking interneurons. Local stimulation of distal dendritic branches within stratum oriens/alveus elicited fast Ca2+ transients, which showed a steep sigmoidal relationship to stimulus intensity. Supralinear Ca2+ events required Ca2+ entry through AMPA receptors with a subsequent Ca2+ release from internal stores. To investigate the functional significance of supralinear Ca2+ signals, we examined activity-dependent fluctuations in transmission efficacy triggered by Ca2+ signals of different amplitudes at excitatory synapses of interneurons. Subthreshold theta-burst stimulation (TBS) produced small amplitude postsynaptic Ca2+ transients and triggered long-term potentiation. In contrast, the suprathreshold TBS, which was associated with the generation of supralinear Ca2+ events, triggered long-term depression. Blocking group I/II metabotropic glutamate receptors (mGluRs) during suprathreshold TBS resulted in a slight reduction of supralinear Ca2+ events and induction of short-term depression. In contrast, blocking internal stores and supralinear Ca2+ signals during suprathreshold TBS switched the direction of plasticity from depression back to potentiation. These data reveal a novel type of supralinear Ca2+ events at synapses lacking the GluA2 AMPA subtype of glutamate receptors and demonstrate a general mechanism by which Ca2+ -permeable AMPA receptors, together with internal stores and mGluRs, control the direction of plasticity at interneuron excitatory synapses.
突触后钙离子（Ca2+）非线性允许神经元的巧合检测和特定部位的可塑性。这种事件是否存在于中间神经元的树突中，并在调节突触效能中发挥作用仍然未知。在这里，我们使用全细胞膜片钳记录和双光子 Ca2+成像的组合，揭示了与小鼠海马 CA1 快速放电中间神经元树突中突触整合相关的 Ca2+非线性。在层状或肺泡内的远端树突分支进行局部刺激，引发快速 Ca2+瞬变，其与刺激强度呈陡峭的 S 型关系。超线性 Ca2+事件需要 AMPA 受体通过 Ca2+进入，随后从内部储存库释放 Ca2+。为了研究超线性 Ca2+信号的功能意义，我们研究了在中间神经元兴奋性突触上不同幅度的 Ca2+信号触发的活动依赖性传递效能波动。阈下θ爆发刺激（TBS）产生小幅度的突触后 Ca2+瞬变，并触发长时程增强。相比之下，阈上 TBS 与超线性 Ca2+事件的产生相关，触发长时程抑制。在阈上 TBS 期间阻断 I/II 型代谢型谷氨酸受体（mGluRs）导致超线性 Ca2+事件略有减少，并诱导短期抑制。相比之下，在阈上 TBS 期间阻断内部储存库和超线性 Ca2+信号将可塑性的方向从抑制切换回增强。这些数据揭示了一种新型的超线性 Ca2+事件，其发生在缺乏 GluA2 AMPA 型谷氨酸受体的突触中，并证明了 Ca2+通透型 AMPA 受体与内部储存库和 mGluRs 一起控制中间神经元兴奋性突触可塑性方向的一般机制。
