Du Xi, Zhang Helen, Parent Jack M
Neuroscience Graduate Program.
Medical Scientist Training Program.
Ann Neurol. 2017 Jun;81(6):790-803. doi: 10.1002/ana.24946.
To understand how monosynaptic inputs onto adult-born dentate granule cells (DGCs) are altered in experimental mesial temporal lobe epilepsy (mTLE) and whether their integration differs from early-born DGCs that are mature at the time of epileptogenesis.
A dual-virus tracing strategy combining retroviral birthdating with rabies virus-mediated putative retrograde trans-synaptic tracing was used to identify and compare presynaptic inputs onto adult-born and early-born DGCs in the rat pilocarpine model of mTLE.
Our results demonstrate that hilar ectopic DGCs preferentially synapse onto adult-born DGCs after pilocarpine-induced status epilepticus (SE), whereas normotopic DGCs synapse onto both adult-born and early-born DGCs. We also find that parvalbumin and somatostatin interneuron inputs are greatly diminished onto early-born DGCs after SE. However, somatostatin interneuron inputs onto adult-born DGCs are maintained, likely due to preferential sprouting. Intriguingly, CA3 pyramidal cell backprojections that specifically target adult-born DGCs arise in the epileptic brain, whereas axons of interneurons and pyramidal cells in CA1 appear to sprout across the hippocampal fissure to preferentially synapse onto early-born DGCs.
These data support the presence of substantial hippocampal circuit remodeling after an epileptogenic insult that generates prominent excitatory monosynaptic inputs, both local recurrent and widespread feedback loops, onto DGCs. Both adult-born and early-born DGCs are targets of new inputs from other DGCs as well as from CA3 and CA1 pyramidal cells after pilocarpine treatment, changes that likely contribute to epileptogenesis in experimental mTLE. Ann Neurol 2017;81:790-803.
了解实验性内侧颞叶癫痫（mTLE）中成年新生齿状颗粒细胞（DGCs）上的单突触输入如何改变，以及它们的整合是否不同于癫痫发生时已成熟的早期新生DGCs。
采用一种双病毒追踪策略，将逆转录病毒出生标记与狂犬病病毒介导的假定逆行跨突触追踪相结合，以识别和比较mTLE大鼠匹鲁卡品模型中成年新生和早期新生DGCs上的突触前输入。
我们的结果表明，在匹鲁卡品诱导的癫痫持续状态（SE）后，门区异位DGCs优先与成年新生DGCs形成突触，而正常位置的DGCs则与成年新生和早期新生DGCs都形成突触。我们还发现，SE后早期新生DGCs上小白蛋白和生长抑素中间神经元的输入大大减少。然而，生长抑素中间神经元对成年新生DGCs的输入得以维持，可能是由于优先发芽。有趣的是，在癫痫脑中出现了专门针对成年新生DGCs的CA3锥体细胞反向投射，而CA1区中间神经元和锥体细胞的轴突似乎穿过海马裂，优先与早期新生DGCs形成突触。
这些数据支持在致痫性损伤后海马回路存在大量重塑，这会在DGCs上产生显著的兴奋性单突触输入，包括局部反复和广泛的反馈回路。在匹鲁卡品处理后，成年新生和早期新生DGCs都是来自其他DGCs以及CA3和CA1锥体细胞新输入的靶点，这些变化可能促成了实验性mTLE中的癫痫发生。《神经病学纪事》2017年；81:790 - 803。
