Activity deprivation reduces miniature IPSC amplitude by decreasing the number of postsynaptic GABAA receptors clustered at neocortical synapses
Activity deprivation reduces miniature IPSC amplitude by decreasing the number of postsynaptic GABAA receptors clustered at neocortical synapses
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DOI：
10.1523/jneurosci.22-04-01328.2002
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发表时间：
2002-02-15
影响因子：
5.3
通讯作者：
Turrigiano, GG
中科院分区：
文献类型：
--
作者：
Kilman, V;van Rossum, MCW;Turrigiano, GG
保持兴奋和抑制之间的适当平衡是必要的，以防止皮层回路陷入沉默或产生癫痫样活动。皮层网络维持这种平衡的一种机制是通过抑制的活动依赖性调节，但这是否主要通过突触数量或突触强度的变化来实现尚不清楚。在此之前，我们发现2d的活动剥夺增加了培养的视皮层锥体神经元上的微型EPSCs（mEPSCs）的振幅。在这里，我们发现这种相同的操作降低了mIPSC的振幅。这在单通道电导没有变化的情况下发生，但伴随着在mIPSC峰期间打开的通道的平均数量的减少和突触后位点处GABA（A）受体（GABA（A）Rs）的染色强度的减少。此外，尽管突触前接触的总数没有减少，但在活动阻断后，表达可检测水平GABA（A）Rs的突触位点的数量减少了近50%。这些数据表明，活动剥夺通过减少聚集在突触部位的GABA（A）R的数量和功能性抑制性突触的数量来减少皮质抑制。由于兴奋性和抑制性突触电流在相反的方向调节活动封锁，这些数据表明，兴奋和抑制之间的平衡是动态调节的持续活动。
Maintaining the proper balance between excitation and inhibition is necessary to prevent cortical circuits from either falling silent or generating epileptiform activity. One mechanism through which cortical networks maintain this balance is through the activity-dependent regulation of inhibition, but whether this is achieved primarily through changes in synapse number or synaptic strength is not clear. Previously, we found that 2 d of activity deprivation increased the amplitude of miniature EPSCs (mEPSCs) onto cultured visual cortical pyramidal neurons. Here we find that this same manipulation decreases the amplitude of mIPSCs. This occurs with no change in single-channel conductance but is accompanied by a reduction in the average number of channels open during the mIPSC peak and a reduction in the intensity of staining for GABA(A) receptors (GABA(A)Rs) at postsynaptic sites. In addition, the number of synaptic sites that express detectable levels of GABA(A)Rs was decreased by similar to50% after activity blockade, although there was no reduction in the total number of presynaptic contacts. These data suggest that activity deprivation reduces cortical inhibition by reducing both the number of GABA(A)Rs clustered at synaptic sites and the number of functional inhibitory synapses. Because excitatory and inhibitory synaptic currents are regulated in opposite directions by activity blockade, these data suggest that the balance between excitation and inhibition is dynamically regulated by ongoing activity.