Department of Neuroscience and Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
Department of Neuroscience and Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
Neuroscience. 2019 Aug 1;412:72-82. doi: 10.1016/j.neuroscience.2019.05.042. Epub 2019 May 30.
Stroke is a devastating brain disorder. The pathophysiology of stroke is associated with an impaired excitation-inhibition balance in the area that surrounds the infarct core after the insult, the peri-infarct zone. Here we exposed slices from adult mouse prefrontal cortex to oxygen-glucose deprivation and reoxygenation (OGD-RO) to study ischemia-induced changes in the activity of excitatory pyramidal neurons and inhibitory parvalbumin (PV)-positive interneurons. We found that during current-clamp recordings, PV-positive interneurons were more vulnerable to OGD-RO than pyramidal neurons as indicated by the lower percentage of recovery of PV-positive interneurons. However, neither the amplitude of OGD-induced depolarization observed in current-clamp mode nor the OGD-associated current observed in voltage-clamp mode differed between the two cell types. Large amplitude, presumably action-potential dependent, spontaneous postsynaptic inhibitory currents recorded from pyramidal neurons were less frequent after OGD-RO than in control condition. Disynaptic inhibitory postsynaptic currents (dIPSCs) in pyramidal neurons produced predominantly by PV-positive interneurons were reduced by OGD-RO. Following OGD-RO, dendrites of PV-positive interneurons exhibited more pathological beading than those of pyramidal neurons. Our data support the hypothesis that the differential vulnerability to ischemia-like conditions of excitatory and inhibitory neurons leads to the altered excitation-inhibition balance associated with stroke pathophysiology.
中风是一种严重的脑部疾病。中风的病理生理学与损伤后梗死核心周围区域（即梗死周边区）的兴奋-抑制平衡受损有关。在这里，我们将成年小鼠前额叶皮层的切片暴露于氧葡萄糖剥夺和再氧合（OGD-RO）中，以研究缺血引起的兴奋性锥体神经元和抑制性 Parvalbumin（PV）阳性中间神经元活性的变化。我们发现，在电流钳记录中，与锥体神经元相比，PV 阳性中间神经元对 OGD-RO 更为敏感，表现为 PV 阳性中间神经元的恢复百分比较低。然而，两种细胞类型之间在电流钳模式下观察到的 OGD 诱导去极化的幅度或在电压钳模式下观察到的 OGD 相关电流没有差异。与对照条件相比，OGD-RO 后从锥体神经元记录到的大振幅、推测与动作电位相关的自发性突触后抑制电流较少。锥体神经元中的由 PV 阳性中间神经元产生的突触后抑制电流（dIPSCs）在 OGD-RO 后减少。OGD-RO 后，PV 阳性中间神经元的树突比锥体神经元表现出更多的病理性珠状。我们的数据支持这样一种假设，即兴奋性和抑制性神经元对类似缺血条件的不同易感性导致与中风病理生理学相关的兴奋-抑制平衡改变。
