Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
CNS Neurosci Ther. 2023 Apr;29(4):1142-1153. doi: 10.1111/cns.14096. Epub 2023 Feb 5.
The relationship between oscillatory activity in hippocampus and cognitive impairment in traumatic brain injury (TBI) remains unclear. Although TBI decreases gamma oscillations and 40 Hz light flicker improves TBI prognosis, the effects and mechanism of rhythmic flicker on TBI remain unclear.
In this study, we aimed to explore whether light flicker could reverse cognitive deficits, and further explore its potential mechanisms in TBI mouse model.
The Morris water maze test (MWM), step-down test (SDT), and novel object recognition test (NOR) were applied to evaluate the cognitive ability. The local field potential (LFP) recording was applied to measure low gamma reduction of CA1 in hippocampus after TBI. And electrophysiological experiments were applied to explore effects of the gamma frequency entrainment on long-term potentiation (LTP), postsynaptic transmission, and intrinsic excitability of CA1 pyramidal cells (PCs) in TBI mice. Immunofluorescence staining and western blotting were applied to explore the effects of 40 Hz light flicker on the expression of PSD95 in hippocampus of TBI mice.
We found that 40 Hz light flicker restored low gamma reduction of CA1 in hippocampus after TBI. And 40 Hz, but not random or 80 Hz light flicker, reversed cognitive impairment after TBI in behavioral tests. Moreover, 40 Hz light flicker improved N-methyl-D-aspartate (NMDA) receptor-dependent LTP (LTP ) and L-type voltage-gated calcium channel-dependent LTP (LTP ) after TBI treatment. And gamma frequency entrainment decreased excitatory postsynaptic currents (EPSCs) of CA1 PCs in TBI mice. Our results have illustrated that 40 Hz light flicker could decrease intrinsic excitability of PCs after TBI treatment in mice. Furthermore, 40 Hz light flicker decreased the expression of PSD95 in hippocampus of TBI mice.
These results demonstrated that 40 Hz light flicker rescues cognitive impairment by decreasing postsynaptic transmission in PCs after TBI treatment in mice.
海马区的震荡活动与创伤性脑损伤（TBI）认知障碍之间的关系尚不清楚。虽然 TBI 会降低伽马震荡，而 40Hz 光闪烁可改善 TBI 预后，但节律性闪烁对 TBI 的影响和机制仍不清楚。
本研究旨在探讨光闪烁是否能逆转认知缺陷，并进一步探索其在 TBI 小鼠模型中的潜在机制。
采用 Morris 水迷宫测试（MWM）、下台阶测试（SDT）和新物体识别测试（NOR）评估认知能力。采用局部场电位（LFP）记录测量 TBI 后海马 CA1 区低伽马减少。电生理实验用于探讨伽马频率同步对 TBI 小鼠 CA1 锥体神经元（PCs）长时程增强（LTP）、突触后传递和固有兴奋性的影响。免疫荧光染色和 Western blot 用于探讨 40Hz 光闪烁对 TBI 小鼠海马 PSD95 表达的影响。
我们发现，40Hz 光闪烁可恢复 TBI 后海马 CA1 区的低伽马减少。40Hz 光闪烁，而不是随机或 80Hz 光闪烁，可逆转 TBI 后的行为学认知障碍。此外，40Hz 光闪烁改善了 TBI 后 N-甲基-D-天冬氨酸（NMDA）受体依赖性 LTP（LTP）和 L 型电压门控钙通道依赖性 LTP（LTP）。伽马频率同步降低了 TBI 小鼠 CA1 PC 的兴奋性突触后电流（EPSCs）。我们的结果表明，40Hz 光闪烁可降低 TBI 后小鼠 CA1 PC 的固有兴奋性。此外，40Hz 光闪烁降低了 TBI 小鼠海马 PSD95 的表达。
这些结果表明，40Hz 光闪烁通过降低 TBI 后小鼠 CA1 PC 的突触后传递来挽救认知障碍。
