Submillisecond firing synchrony between different subtypes of cortical interneurons connected chemically but not electrically.
Submillisecond firing synchrony between different subtypes of cortical interneurons connected chemically but not electrically.
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DOI：
10.1523/jneurosci.4881-10.2011
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发表时间：
2011-03-02
期刊：
影响因子：
--
通讯作者：
Agmon A
中科院分区：
文献类型：
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作者：
Hu H;Ma Y;Agmon A
同步放电在大脑中很常见，但其潜在机制和神经生物学意义仍然存在争议。最常见的是，同步归因于间隙连接的电耦合或共享的兴奋性输入。在大脑皮层和海马体中，快速放电（FS）或含有生长抑素（SOM）的抑制性中间神经元与相同类型的相邻神经元电耦合，并且每个亚型特异性网络往往同步放电。跨亚型的电耦合很弱或不存在，但 SOM-FS 和 FS-FS 对通常通过抑制性突触连接。理论研究表明，纯粹的抑制性耦合也可以促进同步。然而，这尚未得到实验证实。我们在体外记录了小鼠体感皮层中 74 对电非耦合的第 4 层中间神经元，发现通过单向或双向抑制性突触连接的强直去极化 FS-FS 和 SOM-FS 对通常彼此在一毫秒内放电。使用一种新颖的、基于抖动的同步测量方法，我们发现同步性与抑制耦合强度相关。重要的是，同步性对离子型谷氨酸受体拮抗剂有抵抗力，但当 GABAA 受体被阻断时，同步性大大降低，这证实在我们的实验系统中 IPSP 对于同步性来说既是必要的又是充分的。在一对尖峰神经元的计算机模拟中出现了亚毫秒的放电滞后，其中唯一假设的神经元之间的相互作用是通过抑制性突触进行的。我们得出的结论是，皮质中间神经元能够在亚型内部和亚型之间同步，并且亚毫秒级放电协调可以仅通过相互突触抑制来产生，既没有共享输入也没有电耦合。
Synchronous firing is commonly observed in the brain, but its underlying mechanisms and neurobiological meaning remain debated. Most commonly, synchrony is attributed either to electrical coupling by gap junctions or to shared excitatory inputs. In the cerebral cortex and hippocampus, fast-spiking (FS) or somatostatin–containing (SOM) inhibitory interneurons are electrically coupled to same-type neighbors, and each subtype-specific network tends to fire in synchrony. Electrical coupling across subtypes is weak or absent, but SOM-FS and FS-FS pairs are often connected by inhibitory synapses. Theoretical studies suggest that purely inhibitory coupling can also promote synchrony; however, this has not been confirmed experimentally. We recorded from 74 pairs of electrically non-coupled layer 4 interneurons in mouse somatosensory cortex in vitro, and found that tonically depolarized FS-FS and SOM-FS pairs connected by uni- or bidirectional inhibitory synapses often fired within one millisecond of each other. Using a novel, jitter-based measure of synchrony, we found that synchrony correlated with inhibitory coupling strength. Importantly, synchrony was resistant to ionotropic glutamate receptors antagonists but was strongly reduced when GABAA receptors were blocked, confirming that in our experimental system IPSPs were both necessary and sufficient for synchrony. Submillisecond firing lags emerged in a computer simulation of pairs of spiking neurons, in which the only assumed interaction between neurons was by inhibitory synapses. We conclude that cortical interneurons are capable of synchronizing both within and across subtypes, and that submillisecond coordination of firing can arise by mutual synaptic inhibition alone, with neither shared inputs nor electrical coupling.