Synaptic reorganization of inhibitory hilar interneuron circuitry after traumatic brain injury in mice.
Synaptic reorganization of inhibitory hilar interneuron circuitry after traumatic brain injury in mice.
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DOI：
10.1523/jneurosci.0032-11.2011
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发表时间：
2011-05-04
期刊：
影响因子：
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通讯作者：
Smith BN
中科院分区：
文献类型：
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作者：
Hunt RF;Scheff SW;Smith BN
齿状回突触网络的功能可塑性与创伤后癫痫和创伤性脑损伤后认知功能障碍的发展有关，但对抑制回路的潜在致病性变化知之甚少。我们检测了在抑制性神经元亚群中表达增强的绿色荧光蛋白的转基因小鼠中，皮层挫伤脑损伤后8-13周，齿状颗粒细胞的突触抑制和存活的GABA能门部中间神经元的兴奋性。颗粒细胞的全细胞电压钳记录显示，头部受伤后自发和微型IPSC频率减少;成对的脉冲比没有同时发生变化，发现在成对的电刺激门后的颗粒细胞。尽管减少抑制输入颗粒细胞，动作电位和EPSC的频率增加门GABA神经元从同侧的损伤，与对照组或对侧切片。此外，无论是颗粒细胞或CA 3锥体细胞层的谷氨酸光刺激后，在同侧的门GABA神经元损伤检测兴奋性突触活动增加。总之，这些研究结果表明，兴奋驱动幸存的门GABA神经元的锥体细胞和颗粒细胞的会聚输入增强，但颗粒细胞的突触抑制损伤后没有完全恢复。调节门抑制性神经元的电路的这种重新布线可能反映了一种重要的代偿机制，但它也可能通过增加幸存个体中间神经元在控制创伤后齿状回颗粒细胞兴奋性中的相对影响而导致网络不稳定。
Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found in granule cells after paired electrical stimulation of the hilus. Despite reduced inhibitory input to granule cells, action potential and EPSC frequencies were increased in hilar GABA neurons from slices ipsilateral to the injury, versus those from control or contralateral slices. Further, increased excitatory synaptic activity was detected in hilar GABA neurons ipsilateral to the injury after glutamate photostimulation of either the granule cell or CA3 pyramidal cell layers. Together, these findings suggest that excitatory drive to surviving hilar GABA neurons is enhanced by convergent input from both pyramidal and granule cells, but synaptic inhibition of granule cells is not fully restored after injury. This rewiring of circuitry regulating hilar inhibitory neurons may reflect an important compensatory mechanism, but it may also contribute to network destabilization by increasing the relative impact of surviving individual interneurons in controlling granule cell excitability in the posttraumatic dentate gyrus.