Extrasynaptic glutamate receptor activation as cellular bases for dynamic range compression in pyramidal neurons.
Extrasynaptic glutamate receptor activation as cellular bases for dynamic range compression in pyramidal neurons.
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DOI：
10.3389/fphys.2012.00334
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发表时间：
2012
影响因子：
4
通讯作者：
Antic SD
中科院分区：
文献类型：
--
作者：
Oikonomou KD;Short SM;Rich MT;Antic SD
重复性突触刺激克服了星形胶质细胞过程从细胞外空间清除谷氨酸的能力，允许一些树突节段在短时间内淹没在谷氨酸池中。这种动态排列激活位于树突轴上的突触外NMDA受体。我们使用电压敏感和钙敏感染料来探测这个富含谷氨酸的位置的树突功能。过量的谷氨酸在突触外空间实现了重复的突触刺激或谷氨酸离子电渗到锥体神经元的树突。两个连续激活的突触输入产生了一个典型的NMDA尖峰，而五个连续的突触输入产生特征的高原电位，让人想起皮质UP状态。虽然NMDA尖峰加上短暂的钙瞬变高度限制谷氨酸输入网站，树突平台电位伴随着钙内流沿着整个树突分支。一旦启动，谷氨酸介导的树突平台电位不能被负电压脉冲中断。突触外NMDA受体在无棘的细胞隔室中的激活足以启动和支持平台电位。持续去极化事件的唯一要求是一组突触外受体附近的游离谷氨酸过剩。高度非线性的树突棘波（平台电位）在索马以高度次线性的方式叠加，揭示了皮质回路中信号压缩的细胞基础。突触外NMDA受体为锥体神经元提供类似于音频工程中的动态范围压缩的功能。它们限制或减小“大声”的音量（即，强电磁输入）和放大“安静的声音”（即，几乎不超过局部尖峰起始的树突阈值的突触能输入）。我们的数据还解释了为什么连续的皮质UP状态在给定的神经元中具有均匀的振幅。
Repetitive synaptic stimulation overcomes the ability of astrocytic processes to clear glutamate from the extracellular space, allowing some dendritic segments to become submerged in a pool of glutamate, for a brief period of time. This dynamic arrangement activates extrasynaptic NMDA receptors located on dendritic shafts. We used voltage-sensitive and calcium-sensitive dyes to probe dendritic function in this glutamate-rich location. An excess of glutamate in the extrasynaptic space was achieved either by repetitive synaptic stimulation or by glutamate iontophoresis onto the dendrites of pyramidal neurons. Two successive activations of synaptic inputs produced a typical NMDA spike, whereas five successive synaptic inputs produced characteristic plateau potentials, reminiscent of cortical UP states. While NMDA spikes were coupled with brief calcium transients highly restricted to the glutamate input site, the dendritic plateau potentials were accompanied by calcium influx along the entire dendritic branch. Once initiated, the glutamate-mediated dendritic plateau potentials could not be interrupted by negative voltage pulses. Activation of extrasynaptic NMDA receptors in cellular compartments void of spines is sufficient to initiate and support plateau potentials. The only requirement for sustained depolarizing events is a surplus of free glutamate near a group of extrasynaptic receptors. Highly non-linear dendritic spikes (plateau potentials) are summed in a highly sublinear fashion at the soma, revealing the cellular bases of signal compression in cortical circuits. Extrasynaptic NMDA receptors provide pyramidal neurons with a function analogous to a dynamic range compression in audio engineering. They limit or reduce the volume of “loud sounds” (i.e., strong glutamatergic inputs) and amplify “quiet sounds” (i.e., glutamatergic inputs that barely cross the dendritic threshold for local spike initiation). Our data also explain why consecutive cortical UP states have uniform amplitudes in a given neuron.
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影响因子：
3.4
作者：
Dodt, HU;Frick, A;Zieglgänsberger, W
通讯作者：
Zieglgänsberger, W
影响因子：
4.2
作者：
Antic SD;Zhou WL;Moore AR;Short SM;Ikonomu KD
通讯作者：
Ikonomu KD
影响因子：
3.3
作者：
Ballesteros-Yáñez, I;Benavides-Piccione, R;DeFelipe, J
通讯作者：
DeFelipe, J
影响因子：
2.5
作者：
Antic, S;Major, G;Zecevic, D
通讯作者：
Zecevic, D
影响因子：
1.8
作者：
Clatworthy, PL;Chirimuuta, M;Tolhurst, DJ
通讯作者：
Tolhurst, DJ