Different forms of glycine- and GABA(A)-receptor mediated inhibitory synaptic transmission in mouse superficial and deep dorsal horn neurons.
Different forms of glycine- and GABA(A)-receptor mediated inhibitory synaptic transmission in mouse superficial and deep dorsal horn neurons.
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DOI：
10.1186/1744-8069-5-65
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发表时间：
2009-11-18
期刊：
影响因子：
3.3
通讯作者：
Callister RJ
中科院分区：
文献类型：
--
作者：
Anderson WB;Graham BA;Beveridge NJ;Tooney PA;Brichta AM;Callister RJ
脊髓背角浅层(SDH)和深层(DDH)神经元接受来自皮肤、肌肉、关节和内脏的感觉信息。在这两个区域，甘氨酸受体(GlyR)和GABAA受体(GABAARs)参与了突触的快速抑制。对于大鼠，几种类型的GABAAR共存于这两个区域，每种受体类型对抑制音的贡献不同。最近在小鼠的研究中发现了SDH中另一种类型的GlyR，(包含Alpha3亚基)。在SDH和DDH中，不同形式的GlyR对感觉处理的贡献尚不清楚。在这里，我们比较了小鼠(P17-37)SDH和DDH的快速抑制性突触传递在脊髓横切片(L3-L5节段，23°C)上的膜片钳电生理。GlyR介导的mIPSCs分别在74%(25/34)和94%(25/27)的SDH和DDH神经元中检测到。相反，GABAAR介导的mIPSCs在两个区域的几乎所有神经元中均可检测到(93%，14/15和100%，18/18)。SDH和DDH的几个Gly-和GABAAR特性也不同。SDH与DDH相比，GlyR介导的mIPSC幅值较小(37.1±3.9对64.7±5.0 pA；n=25)，衰减时间较慢(8.5±0.8对5.5±0.3 ms)，频率较低(0.15±0.03对0.72±0.13 Hz)。相反，GABAAR介导的mIPSCs的波幅相似(25.6±2.4，n=14比25)。和频率(0.21±0.08对0.18±0.04赫兹)，但SDH神经元的衰减时间较慢(23.0±3.2对18.9±1.8ms)。GlyRs(54.3±1.6pS，n=11 vs.55.7±1.8，n=8)和GABAARs(22.7±1.7pS，n=10 vs.22.4±2.0pS，n=11)在两个区域的平均单通道电导相同。我们还测试了合成的内源性类胡萝卜素--甲基安非他胺是否对每个脊髓区域的Gly-和GABAARs有直接影响。方法AEA(5μM)可降低GlyR介导的mIPSC在SDH和DDH中的频率，但不影响其他特性。在GABAAR介导的mIPSCs中也观察到了类似的结果，但在SDH神经元上，甲基AEA减缓了上升时间。总之，这些数据表明，具有明显不同生理特性和大麻素敏感性的Gly-和GABAARs有助于小鼠SDH和DDH的快速突触抑制。
Neurons in superficial (SDH) and deep (DDH) laminae of the spinal cord dorsal horn receive sensory information from skin, muscle, joints and viscera. In both regions, glycine- (GlyR) and GABAA-receptors (GABAARs) contribute to fast synaptic inhibition. For rat, several types of GABAAR coexist in the two regions and each receptor type provides different contributions to inhibitory tone. Recent work in mouse has discovered an additional type of GlyR, (containing alpha 3 subunits) in the SDH. The contribution of differing forms of the GlyR to sensory processing in SDH and DDH is not understood. Here we compare fast inhibitory synaptic transmission in mouse (P17-37) SDH and DDH using patch-clamp electrophysiology in transverse spinal cord slices (L3-L5 segments, 23°C). GlyR-mediated mIPSCs were detected in 74% (25/34) and 94% (25/27) of SDH and DDH neurons, respectively. In contrast, GABAAR-mediated mIPSCs were detected in virtually all neurons in both regions (93%, 14/15 and 100%, 18/18). Several Gly- and GABAAR properties also differed in SDH vs. DDH. GlyR-mediated mIPSC amplitude was smaller (37.1 ± 3.9 vs. 64.7 ± 5.0 pA; n = 25 each), decay time was slower (8.5 ± 0.8 vs. 5.5 ± 0.3 ms), and frequency was lower (0.15 ± 0.03 vs. 0.72 ± 0.13 Hz) in SDH vs. DDH neurons. In contrast, GABAAR-mediated mIPSCs had similar amplitudes (25.6 ± 2.4, n = 14 vs. 25. ± 2.0 pA, n = 18) and frequencies (0.21 ± 0.08 vs. 0.18 ± 0.04 Hz) in both regions; however, decay times were slower (23.0 ± 3.2 vs. 18.9 ± 1.8 ms) in SDH neurons. Mean single channel conductance underlying mIPSCs was identical for GlyRs (54.3 ± 1.6 pS, n = 11 vs. 55.7 ± 1.8, n = 8) and GABAARs (22.7 ± 1.7 pS, n = 10 vs. 22.4 ± 2.0 pS, n = 11) in both regions. We also tested whether the synthetic endocanabinoid, methandamide (methAEA), had direct effects on Gly- and GABAARs in each spinal cord region. MethAEA (5 μM) reduced GlyR-mediated mIPSC frequency in SDH and DDH, but did not affect other properties. Similar results were observed for GABAAR mediated mIPSCs, however, rise time was slowed by methAEA in SDH neurons. Together these data show that Gly- and GABAARs with clearly differing physiological properties and cannabinoid-sensitivity contribute to fast synaptic inhibition in mouse SDH and DDH.
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