Camiré Olivier, Lazarevich Ivan, Gilbert Tommy, Topolnik Lisa
Department of Biochemistry, Microbiology and Bio-informatics, Faculty of Science and Engineering; Neuroscience Axis, CHU de Québec Research Center (CHUL), Laval University, Québec, QC, Canada.
Lobachevsky State University of Nizhni Novgorod, Nizhny Novgorod, Russia.
Front Synaptic Neurosci. 2018 Dec 11;10:47. doi: 10.3389/fnsyn.2018.00047. eCollection 2018.
In fast-spiking (FS), parvalbumin-expressing interneurons of the CA1 hippocampus, activation of the GluA2-lacking Ca-permeable AMPA receptors (CP-AMPARs) in basal dendrites is coupled to Ca-induced Ca-release (CICR), and can result in a supralinear summation of postsynaptic Ca-transients (post-CaTs). While this mechanism is important in controlling the direction of long-term plasticity, it is still unknown whether it can operate at all excitatory synapses converging onto FS cells or at a set of synapses receiving a particular input. Using a combination of patch-clamp recordings and two-photon Ca imaging in acute mouse hippocampal slices with computational simulations, here we compared the generation of supralinear post-CaTs between apical and basal dendrites of FS cells. We found that, similar to basal dendrites, apical post-CaTs summated supralinearly and relied mainly on the activation of the CP-AMPARs, with a variable contribution of other Ca sources, such as NMDA receptors, L-type voltage-gated Ca-channels and Ca release. In addition, supralinear post-CaTs generated in apical dendrites had a slower decay time and a larger cumulative charge than those in basal, and were associated with a stronger level of somatic depolarization. The model predicted that modulation of ryanodine receptors and of the Ca extrusion mechanisms, such as the Na/Ca-exchanger and SERCA pump, had a major impact on the magnitude of supralinear post-CaTs. These data reveal that supralinear Ca summation is a common mechanism of Ca signaling at CP-AMPAR-containing synapses. Shaped in a location-specific manner through modulation of ryanodine receptors and Ca extrusion mechanisms, CP-AMPAR/CICR signaling is suitable for synapse-specific bidirectional modification of incoming inputs in the absence of active dendritic conductances.
在海马体CA1区快速放电（FS）且表达小白蛋白的中间神经元中，基底树突中缺乏GluA2的钙通透性AMPA受体（CP-AMPARs）的激活与钙诱导的钙释放（CICR）相关联，并可导致突触后钙瞬变（post-CaTs）的超线性总和。虽然这种机制在控制长期可塑性的方向方面很重要，但尚不清楚它是否能在汇聚到FS细胞上的所有兴奋性突触处起作用，或者在一组接受特定输入的突触处起作用。在这里，我们结合急性小鼠海马切片中的膜片钳记录和双光子钙成像以及计算模拟，比较了FS细胞顶端和基底树突中超线性post-CaTs的产生情况。我们发现，与基底树突类似，顶端post-CaTs也进行超线性总和，并且主要依赖于CP-AMPARs的激活，其他钙源（如NMDA受体、L型电压门控钙通道和钙释放）也有不同程度的贡献。此外，顶端树突中产生的超线性post-CaTs的衰减时间较慢，累积电荷量比基底树突中的更大，并且与更强的体细胞去极化水平相关。该模型预测，雷诺丁受体以及钙外排机制（如钠/钙交换器和肌浆网钙ATP酶泵）的调节对超线性post-CaTs的大小有重大影响。这些数据表明，超线性钙总和是含CP-AMPAR突触处钙信号传导的常见机制。通过对雷诺丁受体和钙外排机制的调节，以位置特异性方式形成的CP-AMPAR/CICR信号传导适用于在无活性树突电导的情况下对传入输入进行突触特异性双向修饰。
