Neuroscience Graduate Program, Vollum Institute, Oregon Health & Science University, Portland, OR 97239.
Department of Anesthesiology and Perioperative Medicine; Oregon Health & Science University, Portland, OR 97239.
Proc Natl Acad Sci U S A. 2019 May 28;116(22):10994-10999. doi: 10.1073/pnas.1821227116. Epub 2019 May 13.
In temporal lobe epilepsy, sprouting of hippocampal mossy fiber axons onto dentate granule cell dendrites creates a recurrent excitatory network. However, unlike mossy fibers projecting to CA3, sprouted mossy fiber synapses depress upon repetitive activation. Thus, despite their proximal location, relatively large presynaptic terminals, and ability to excite target neurons, the impact of sprouted mossy fiber synapses on hippocampal hyperexcitability is unclear. We find that despite their short-term depression, single episodes of sprouted mossy fiber activation in hippocampal slices initiated bursts of recurrent polysynaptic excitation. Consistent with a contribution to network hyperexcitability, optogenetic activation of sprouted mossy fibers reliably triggered action potential firing in postsynaptic dentate granule cells after single light pulses. This pattern resulted in a shift in network recruitment dynamics to an "early detonation" mode and an increased probability of release compared with mossy fiber synapses in CA3. A lack of tonic adenosine-mediated inhibition contributed to the higher probability of glutamate release, thus facilitating reverberant circuit activity.
在颞叶癫痫中，海马苔藓纤维轴突在齿状回颗粒细胞树突上的发芽形成了一个复发性兴奋性网络。然而，与投射到 CA3 的苔藓纤维不同，发芽的苔藓纤维突触在重复激活时会抑制。因此，尽管发芽的苔藓纤维突触位于近端位置，具有较大的突触前末梢，并且能够兴奋靶神经元，但它们对海马过度兴奋的影响尚不清楚。我们发现，尽管发芽的苔藓纤维激活具有短期抑制作用，但海马切片中单发性发芽苔藓纤维激活会引发复发性多突触兴奋的爆发。与对网络过度兴奋的贡献一致，光遗传激活发芽的苔藓纤维在单个光脉冲后可靠地触发了突触后齿状回颗粒细胞的动作电位放电。这种模式导致网络募集动力学向“早期爆炸”模式转变，并且与 CA3 中的苔藓纤维突触相比，释放的概率增加。缺乏持续的腺苷介导的抑制作用导致谷氨酸释放的概率增加，从而促进了回响电路活动。
