DOC2B and Munc13-1 differentially regulate neuronal network activity.
DOC2B and Munc13-1 differentially regulate neuronal network activity.
复制标题
DOC2B 和 Munc13-1 差异调节神经元网络活动。
DOI：
10.1093/cercor/bht081
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Ashery,Uri
中科院分区：
文献类型：
--
作者：
Lavi,Ayal;Sheinin,Anton;Shapira,Ronit;Zelmanoff,Daniel;Ashery,Uri
突触蛋白水平的改变影响突触传递和突触可塑性。然而，对神经元网络活动的确切影响仍然是个谜。在这里，我们利用微电极阵列（MEA）来阐明突触前释放过程的操纵如何影响神经元网络的活动。通过结合药理学工具和突触蛋白的遗传操作，我们发现，DOC 2B和Munc 13 -1，已知促进囊泡成熟和释放的蛋白质的过表达，对神经元网络的活性产生相反的影响。虽然两者都导致尖峰总数的增加，但尖峰的分布是不同的。虽然DOC 2B增强，但Munc 13 -1降低了整个网络中尖峰突发内的放电速率;然而，Munc 13 -1增加了网络突发的速率。增加异步释放的锶模拟了DOC 2B的作用，但增加自发释放速率的DOC 2B突变体没有模拟DOC 2B的作用。这首次表明，在单个神经元水平上增加异步释放会促进网络水平上的爆发活动。这项创新的研究表明，网络水平的补充作用，解释突触前蛋白的细胞活性的生理相关性和突触释放操纵从神经元到网络水平的转变。
Alterations in the levels of synaptic proteins affect synaptic transmission and synaptic plasticity. However, the precise effects on neuronal network activity are still enigmatic. Here, we utilized microelectrode array (MEA) to elucidate how manipulation of the presynaptic release process affects the activity of neuronal networks. By combining pharmacological tools and genetic manipulation of synaptic proteins, we show that overexpression of DOC2B and Munc13-1, proteins known to promote vesicular maturation and release, elicits opposite effects on the activity of the neuronal network. Although both cause an increase in the overall number of spikes, the distribution of spikes is different. While DOC2B enhances, Munc13-1 reduces the firing rate within bursts of spikes throughout the network; however, Munc13-1 increases the rate of network bursts. DOC2B's effects were mimicked by Strontium that elevates asynchronous release but not by a DOC2B mutant that enhances spontaneous release rate. This suggests for the first time that increased asynchronous release on the single-neuron level promotes bursting activity in the network level. This innovative study demonstrates the complementary role of the network level in explaining the physiological relevance of the cellular activity of presynaptic proteins and the transformation of synaptic release manipulation from the neuron to the network level.