Complex events initiated by individual spikes in the human cerebral cortex.

Complex events initiated by individual spikes in the human cerebral cortex.
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DOI:
10.1371/journal.pbio.0060222
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发表时间:
2008-09-02
期刊:
影响因子:
9.8
通讯作者:
Tamás G
Tamás G
中科院分区:
生物学1区
文献类型:
--
作者:
Molnár G;Oláh S;Komlósi G;Füle M;Szabadics J;Varga C;Barzó P;Tamás G

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迄今为止,人类大脑皮层神经元之间的突触相互作用还没有直接研究过。据我们所知,我们记录了第一个数据集,关于已识别的人类锥体细胞对各种类型的突触后神经元的突触效应,并揭示了人类新皮层网络中由个体动作电位触发的复杂事件。脑切片是从58名年龄在18 - 73岁的患者的联合皮质下的脑区的手术治疗中必须切除的非病理性皮质样品制备的。同时进行三重和四重全细胞膜片钳记录,测试靶神经元中的单突触和多突触电位,然后由第2/3层锥体细胞激发单个动作电位,并分析事件的时间结构和潜在机制。除了单突触突触后电位外,突触前锥体细胞中的个体动作电位还引发了网络中持续时间较长(37 ± 17 ms)的事件序列,持续时间比以前在其他物种中检测到的时间长一个数量级。这些事件系列由特异性交替的谷氨酸能和GABA能突触后电位组成,需要从锥体细胞到GABA能中间神经元的选择性尖峰-尖峰耦合,产生伴随的GABA的抑制性和兴奋性前馈作用。人类神经元的单个动作电位足以招募被提议参与认知过程的Hebbian样神经元组装体。据我们所知,我们记录了人类神经细胞之间的第一个连接,并揭示了一个子集的相互作用是如此强烈,以至于一些突触前细胞能够在突触后靶神经元中引发动作电位。有趣的是,这些强连接选择性地将使用神经递质谷氨酸的锥体细胞与释放伽马氨基丁酸(GABA)的神经元连接起来。此外,接收强连接的GABA能神经元包括不同类型:篮状细胞,其抑制几个靶细胞群,以及另一种称为枝形细胞的类型,其可以是兴奋性的并且仅靶向锥体细胞。因此,源自单个锥体细胞的激活传播到同步工作的抑制性和兴奋性GABA能神经元。然后,抑制到达各种神经元类别,但兴奋只找到锥体细胞,这反过来又可以在神经元网络中进一步传播兴奋。这里揭示的这一系列事件导致网络激活的时间比以前在单个神经元中响应单个动作电位时检测到的时间长大约一个数量级。单个神经元激活的神经元组类似于所谓的功能组件,被认为是高阶认知表征的构建块。一项关于人类神经元之间连接的新研究表明,锥体细胞中的单个棘波可以通过连接锥体细胞与抑制性和兴奋性GABA能神经元的强连接激活同步定时组装。
Synaptic interactions between neurons of the human cerebral cortex were not directly studied to date. We recorded the first dataset, to our knowledge, on the synaptic effect of identified human pyramidal cells on various types of postsynaptic neurons and reveal complex events triggered by individual action potentials in the human neocortical network. Brain slices were prepared from nonpathological samples of cortex that had to be removed for the surgical treatment of brain areas beneath association cortices of 58 patients aged 18 to 73 y. Simultaneous triple and quadruple whole-cell patch clamp recordings were performed testing mono- and polysynaptic potentials in target neurons following a single action potential fired by layer 2/3 pyramidal cells, and the temporal structure of events and underlying mechanisms were analyzed. In addition to monosynaptic postsynaptic potentials, individual action potentials in presynaptic pyramidal cells initiated long-lasting (37 ± 17 ms) sequences of events in the network lasting an order of magnitude longer than detected previously in other species. These event series were composed of specifically alternating glutamatergic and GABAergic postsynaptic potentials and required selective spike-to-spike coupling from pyramidal cells to GABAergic interneurons producing concomitant inhibitory as well as excitatory feed-forward action of GABA. Single action potentials of human neurons are sufficient to recruit Hebbian-like neuronal assemblies that are proposed to participate in cognitive processes. We recorded the first connections, to our knowledge, between human nerve cells and reveal that a subset of interactions is so strong that some presynaptic cells are capable of eliciting action potentials in the postsynaptic target neurons. Interestingly, these strong connections selectively link pyramidal cells using the neurotransmitter glutamate to neurons releasing gamma aminobutyric acid (GABA). Moreover, the GABAergic neurons receiving the strong connections include different types: basket cells, which inhibit several target cell populations, and another type called the chandelier cells, which can be excitatory and target pyramidal cells only. Thus, the activation originating from a single pyramidal cell propagates to synchronously working inhibitory and excitatory GABAergic neurons. Inhibition then arrives to various neuron classes, but excitation finds only pyramidal cells, which in turn, can propagate excitation even further in the network of neurons. This chain of events revealed here leads to network activation approximately an order of magnitude longer than detected previously in response to a single action potential in a single neuron. Individual-neuron–activated groups of neurons resemble the so-called functional assemblies that were proposed as building blocks of higher order cognitive representations. A novel study on connections between human neurons reveals that single spikes in pyramidal cells can activate synchronously timed assemblies through strong connections linking pyramidal cells with inhibitory and excitatory GABAergic neurons.
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