Decrease in Tonic Inhibition Contributes to Increase in Dentate Semilunar Granule Cell Excitability after Brain Injury
Decrease in Tonic Inhibition Contributes to Increase in Dentate Semilunar Granule Cell Excitability after Brain Injury
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DOI：
10.1523/jneurosci.4141-11.2012
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发表时间：
2012-02-15
影响因子：
5.3
通讯作者：
Santhakumar, Vijayalakshmi
中科院分区：
文献类型：
--
作者：
Gupta, Akshay;Elgammal, Fatima S.;Santhakumar, Vijayalakshmi
脑损伤是颞叶癫痫的病因之一，可导致记忆和认知障碍。最近的特点是兴奋性神经元类的齿状分子层，半月颗粒细胞（SGC），已被提出来调节齿状网络的活动模式和工作记忆的形成。虽然SGCs，像颗粒细胞，项目CA3，其典型的持续放电和关联轴突侧支表明，他们是功能上不同于颗粒细胞。我们发现，脑损伤后1周，与输入阻力增加相关的SGC兴奋性增强。除了延长微小和自发的IPSC间期外，脑损伤还显著降低了SGCs的紧张性GABA电流的幅度。损伤后SGC紧张性GABA电流的减少与创伤后颗粒细胞中观察到的增加形成直接对比。虽然我们观察到SGCs表达Prox 1表明与颗粒细胞有共同的谱系，但对照大鼠的数据显示，SGCs强直性GABA电流较大，sIPSC间期较颗粒细胞短，表明这些细胞类型之间抑制的内在差异。GABA（A）受体拮抗剂选择性地增加对照组而非脑损伤大鼠的SGC输入阻力。此外，创伤后SGC放电的差异在GABAA受体阻滞剂中被消除。我们的数据表明，细胞类型特异性的创伤后紧张性GABA电流减少会增强脑损伤后的SGC兴奋性。过度兴奋的SGCs可以增加齿状回对CA3的转运，并实质性地增加创伤性脑损伤后癫痫和记忆功能障碍的风险。
Brain injury is an etiological factor for temporal lobe epilepsy and can lead to memory and cognitive impairments. A recently characterized excitatory neuronal class in the dentate molecular layer, semilunar granule cell (SGC), has been proposed to regulate dentate network activity patterns and working memory formation. Although SGCs, like granule cells, project to CA3, their typical sustained firing and associational axon collaterals suggest that they are functionally distinct from granule cells. We find that brain injury results in an enhancement of SGC excitability associated with an increase in input resistance 1 week after trauma. In addition to prolonging miniature and spontaneous IPSC interevent intervals, brain injury significantly reduces the amplitude of tonic GABA currents in SGCs. The postinjury decrease in SGC tonic GABA currents is in direct contrast to the increase observed in granule cells after trauma. Although our observation that SGCs express Prox1 indicates a shared lineage with granule cells, data from control rats show that SGC tonic GABA currents are larger and sIPSC interevent intervals shorter than in granule cells, demonstrating inherent differences in inhibition between these cell types. GABA(A) receptor antagonists selectively augmented SGC input resistance in controls but not in head-injured rats. Moreover, post-traumatic differences in SGC firing were abolished in GABAA receptor blockers. Our data show that cell-type-specific post-traumatic decreases in tonic GABA currents boost SGC excitability after brain injury. Hyperexcitable SGCs could augment dentate throughput to CA3 and contribute substantively to the enhanced risk for epilepsy and memory dysfunction after traumatic brain injury.