Restrictions on inhibitory circuits contribute to limited recruitment of fast inhibition in rat neocortical pyramidal cells

Restrictions on inhibitory circuits contribute to limited recruitment of fast inhibition in rat neocortical pyramidal cells
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DOI:
10.1152/jn.1999.82.4.1793
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发表时间:
1999-10-01
影响因子:
2.5
通讯作者:
Benardo, LS
Benardo, LS
中科院分区:
医学3区
文献类型:
--
作者:
Ling, DSF;Benardo, LS

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抑制回路的限制导致大鼠新皮层锥体细胞快速抑制的有限招募。神经生理学杂志。82:1793-1807,1999.为了进一步定义新皮层中快速抑制的操作边界,从新皮层切片中的第V层锥体神经元进行全细胞记录以评估诱发的抑制性突触后电流(IPSC)和自发的微型IPSC(mIPSC)。将刺激电极放置在VI层和I/II层中,以确定同时刺激深层和浅层是否可以延长单独深层刺激诱发的最大IPSC的幅度。此外,浅层刺激并没有增加最大IPSC振幅,证实了对快速抑制的严格限制。在河豚毒素的存在下记录自发的微型IPSC。自发mIPSC的频率范围为10.0至33.1 Hz。mIPSC振幅变化相当大,范围为5.0-128.2 pA,平均值为20.7 +/- 4.1 pA(n = 12个细胞)。微型IPSC的衰减阶段最适合由一个单一的指数,类似于诱发IPSC。平均衰减时间常数为6.4 +/- 0.6 ms,范围为0.2-20.1 ms。平均10-90%上升时间为1.9 +/- 0.2 ms,范围为0.2至6.3 ms。mIPSC动力学评估显示没有树枝状过滤的证据。mIPSC的振幅直方图显示出具有几个可辨别的峰的偏斜分布,当与高斯曲线拟合时,这些峰似乎是等距间隔的,这表明mIPSC振幅在数量上变化。高斯峰的平均分离范围为6.1至7.8 pA。量子分布似乎不是噪声的伪影。暴露于含有低Ca 2+和高Mg 2+浓度的盐水减少了直方图峰的数量,但不影响量子尺寸。平均mIPSC振幅和量子尺寸以接近线性的方式随细胞保持电位变化。振幅直方图的统计评价验证了mIPSC振幅分布的多模态性,并证实了峰的等距间距。mIPSC值与来自单个GABA通道记录的公开数据的比较表明,平均mIPSC电导对应于10-20个GABA受体通道的激活,并且单个抑制量子的释放打开3-6个通道。mIPSC与诱发的抑制事件的进一步比较表明,单个中间神经元可以与锥体细胞形成平均4-12个功能性突触,并且在最大群体IPSC的募集期间,10-12个单独的中间神经元参与。这表明,抑制回路的单位事件的大小和有效连接数相比,兴奋性输入时,更受限制。
Restrictions on inhibitory circuits contribute to limited recruitment of fast inhibition in rat neocortical pyramidal cells. J. Neurophysiol. 82: 1793-1807, 1999. To further define the operational boundaries on fast inhibition in neocortex, whole cell recordings were made from layer V pyramidal neurons in neocortical slices to evaluate evoked inhibitory postsynaptic currents (IPSCs) and spontaneous miniature IPSCs (mIPSCs). Stimulating electrodes were placed in layers VI and I/II to determine whether simultaneous stimulation of deep and superficial laminae could extend the magnitude of maximal IPSCs evoked by deep-layer stimulation alone. The addition of superficial-layer stimulation did not increase maximal IPSC amplitude, confirming the strict limit on fast inhibition. Spontaneous miniature IPSCs were recorded in the presence of tetrodotoxin. The frequency of spontaneous mIPSCs ranged from 10.0 to 33.1 Hz. mIPSC amplitude varied considerably, with a range of 5.0-128.2 pA and a mean value of 20.7 +/- 4.1 pA (n = 12 cells). The decay phase of miniature IPSCs was best fit by a single exponential, similar to evoked IPSCs. The mean time constant of decay was 6.4 +/- 0.6 ms, with a range of 0.2-20.1 ms. The mean 10-90% rise time was 1.9 +/- 0.2 ms, ranging from 0.2 to 6.3 ms. Evaluation of mIPSC kinetics revealed no evidence of dendritic filtering. Amplitude histograms of mIPSCs exhibited skewed distributions with several discernable peaks that, when fit with Gaussian curves, appeared to be spaced equidistantly, suggesting that mIPSC amplitudes varied quantally. The mean separation of Gaussian peaks ranged from 6.1 to 7.8 pA. The quantal distributions did not appear to be artifacts of noise. Exposure to saline containing low Ca2+ and high Mg2+ concentrations reduced the number of histogram peaks, but did not affect the quantal size, Mean mIPSC amplitude and quantal size varied with cell holding potential in a near-linear manner. Statistical evaluation of amplitude histograms verified the multimodality of mIPSC amplitude distributions and corroborated the equidistant spacing of peaks. Comparison of mIPSC values with published data from single GABA channel recordings suggests that the mean mIPSC conductance corresponds to the activation of 10-20 GABA, receptor channels, and that the release of a single inhibitory quantum opens 3-6 channels. Further comparison of mIPSCs with evoked inhibitory events suggests that a single interneuron may form, on average, 4-12 functional synapses with a pyramidal cell, and that 10-12 individual interneurons are engaged during recruitment of maximal population IPSCs. This suggests that inhibitory circuits are much more restricted in both the size of the unit events and effective number of connections when compared with excitatory inputs.