Two Forms of Synaptic Depression Produced by Differential Neuromodulation of Presynaptic Calcium Channels
Two Forms of Synaptic Depression Produced by Differential Neuromodulation of Presynaptic Calcium Channels
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DOI：
10.1016/j.neuron.2018.07.030
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发表时间：
2018-09-05
期刊：
影响因子：
16.2
通讯作者：
Bender, Kevin J.
中科院分区：
文献类型：
--
作者：
Burke, Kenneth J., Jr.;Keeshen, Caroline M.;Bender, Kevin J.
神经调质是整个大脑中突触传递的重要调节器。在突触前末梢，钙通道（CaVs）的神经调节不仅可以通过改变神经递质释放概率，而且可以通过塑造短期可塑性（STP）来影响传递。事实上，STP的变化通常被认为是定义突触前作用部位的一个必要条件。然而，一些突触表现出非规范形式的神经调节，其中释放概率改变而STP没有相应的变化。在这里，我们确定的生物物理机制，规范和非规范突触前神经调制可以发生在同一个突触。在前额叶皮层的多巴胺能末梢的一个子集，GABA（B）和D1/D5多巴胺受体通过调节突触前CaV功能的不同方面抑制释放概率，无论是否有短期易化的典型增加。这些发现建立了一个框架，使来自多种神经调质的信号可以汇聚在突触前CaV上，以差异化地调节同一突触的释放动力学。
Neuromodulators are important regulators of synaptic transmission throughout the brain. At the presynaptic terminal, neuromodulation of calcium channels (CaVs) can affect transmission not only by changing neurotransmitter release probability, but also by shaping short-term plasticity (STP). Indeed, changes in STP are often considered a requirement for defining a presynaptic site of action. Nevertheless, some synapses exhibit non-canonical forms of neuromodulation, where release probability is altered without a corresponding change in STP. Here, we identify biophysical mechanisms whereby both canonical and non-canonical presynaptic neuromodulation can occur at the same synapse. At a subset of glutamatergic terminals in prefrontal cortex, GABA(B) and D1/D5 dopamine receptors suppress release probability with and without canonical increases in short-term facilitation by modulating different aspects of presynaptic CaV function. These findings establish a framework whereby signaling from multiple neuromodulators can converge on presynaptic CaVs to differentially tune release dynamics at the same synapse.