Spontaneous GABA(A) receptor-mediated inhibitory currents in adult rat somatosensory cortex
Spontaneous GABA(A) receptor-mediated inhibitory currents in adult rat somatosensory cortex
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DOI：
10.1152/jn.1996.75.4.1573
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发表时间：
1996-04-01
影响因子：
2.5
通讯作者：
Prince, DA
中科院分区：
文献类型：
--
作者：
Salin, PA;Prince, DA
1.用全细胞电压钳技术研究了成年大鼠皮层体感脑片131个锥体细胞的自发抑制性突触电流（sIPSCs）。用生物胞素对神经元进行细胞内标记，并根据其胞体的层状定位将其分类为颗粒上（SG，层2-3）、层IV（IV）或颗粒下（IG，层V）。SG、IV和IG神经元的躯体区域相似。所有鉴定的锥体细胞均产生高频率的γ-氨基丁酸（GABA（A））受体介导的突触事件.荷包牡丹碱的浴用阻断了sIPSCs，并导致静息电导下降约0.5 nS，基线电流向内偏移。SG神经元的sIPSC频率显著低于IG或TV神经元，这种差异是由于IG和IV神经元中sIPSC爆发的百分比较高.α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂6-氰基-7-硝基喹喔啉-2，3-二酮（CNQX）的浴用使sIPSC的频率降低了13- 21%。相比之下，应用N-甲基-D-天冬氨酸（NMDA）受体拮抗剂D-2-氨基-5-膦酰基戊酸（D-AP 5）对自发IPSC频率没有影响，表明AMPA而不是NMDA受体激活促进了抑制性中间神经元的静息放电。向灌注介质中加入河豚毒素（TTX）可使自发IPSC频率降低约30- 55%。在含有TTX的溶液中看到的微型IPSC（mIPSCS）具有类似于10 Hz的频率和0.42-0.48 nS的平均电导。6.在不同层锥体细胞中产生的mIPSC的动力学性质是相同的，在保持电位为0 mV时，上升时间近似为0.9ms，衰减时间常数近似为8 ms。mIPSC的衰减阶段通常由一个指数拟合，并且显示出电压依赖性，对于每198-mV的去极化，衰减时间常数增加e倍。这些结果表明，有正在进行的自发释放GABA的新皮层切片，引起高频脉冲相关和非脉冲相关的突触后抑制电流。抑制性中间神经元上AMPA受体的激活仅占GABA（A）受体介导的事件的一小部分。从mIPSC频率在不同板层神经元中的分布来看，在整个皮层中存在相对均匀的抑制性突触分布。新皮质锥体神经元上GABA（A）受体的紧张性激活会增加静息膜电导，这可能通过防止过度兴奋性的发展、调节兴奋性突触事件以及控制棘波放电的速率和模式在体内发挥重要作用。
1. Spontaneous inhibitory synaptic currents (sIPSCs) were studied with whole cell voltage-clamp recordings from 131 pyramidal cells in adult rat somatosensory cortical slices. Neurons were intracellulary labeled with biocytin and classified as supragranular (SG, layers 2-3), layer IV (IV), or infragranular (IG, layer V) on the basis of the laminar localization of their somata. Somatic areas were similar for SG, IV, and IG neurons. All identified pyramidal cells generated high-frequency gamma-aminobutyric acid (GABA(A)) receptor-mediated synaptic events.2. Bath application of bicuculline blocked the sIPSCs and re suited in a decrease of similar to 0.5 nS in resting conductance and an inward shift in baseline current.3. sIPSC frequency was significantly lower in SG versus IG or TV neurons, and this difference was accounted for by the occurrence of a higher percentage of bursts of sIPSCs in the IG and IV neurons.4. Bath application of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproptionic (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) decreased the frequency of sIPSCs by 13-21%. By contrast, application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-AP5) generally had no effect on spontaneous IPSC frequency, suggesting that AMPA rather than NMDA receptor activation contributed to resting discharge of inhibitory interneurons.5. Addition of tetrodotoxin (TTX) to the perfusion medium reduced the spontaneous IPSC frequency by similar to 30-55%. The miniature IPSCs (mIPSCS) Seen in TTX-containing solutions had a frequency of similar to 10 Hz and an average conductance of 0.42-0.48 nS.6. The kinetic properties of mIPSCs generated in pyramidal cells of different layers were the same, with the rise times of similar to 0.9 ms and decay time constants of similar to 8 ms at a holding potential of 0 mV. The decay phase of mIPSCs was generally fitted by one exponential and displayed a voltage dependence with an e-fold increase in decay time constant for a every 198-mV depolarization.7. These results show that there is ongoing spontaneous release of GABA in neocortical slices that gives rise to high-frequency impulse-related and non-impulse-related postsynaptic inhibitory currents. Activation of AMPA receptors on inhibitory interneurons accounts for only a small proportion of the GABA(A) receptor-mediated events. Judging from the distribution of mIPSC frequencies in neurons of different laminae, there is a relatively uniform distribution of inhibitory synapses throughout the cortex. Tonic activation of GABA(A) receptors on neocortical pyramidal neurons generates an increase in resting membrane conductance that may play an important role in vivo by preventing the development of hyperexcitability, modulating excitatory synaptic events, and controlling the rate and patterns of spike discharge.