Cranial irradiation impairs intrinsic excitability and synaptic plasticity of hippocampal CA1 pyramidal neurons with implications for cognitive function.

Radiation therapy is a standard treatment for head and neck tumors. However, patients often exhibit cognitive impairments following radiation therapy. Previous studies have revealed that hippocampal dysfunction, specifically abnormal hippocampal neurogenesis or neuroinflammation, plays a key role in radiation-induced cognitive impairment. However, the long-term effects of radiation with respect to the electrophysiological adaptation of hippocampal neurons remain poorly characterized. We found that mice exhibited cognitive impairment 3 months after undergoing 10 minutes of cranial irradiation at a dose rate of 3 Gy/min. Furthermore, we observed a remarkable reduction in spike firing and excitatory synaptic input, as well as greatly enhanced inhibitory inputs, in hippocampal CA1 pyramidal neurons. Corresponding to the electrophysiological adaptation, we found reduced expression of synaptic plasticity marker VGLUT1 and increased expression of VGAT. Furthermore, in irradiated mice, long-term potentiation in the hippocampus was weakened and GluR1 expression was inhibited. These findings suggest that radiation can impair intrinsic excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.

放射治疗是头颈部肿瘤的一种标准治疗方法。然而，患者在放射治疗后常出现认知障碍。先前的研究表明，海马功能障碍，特别是异常的海马神经发生或神经炎症，在放射性认知障碍中起着关键作用。然而，关于辐射对海马神经元电生理适应性的长期影响，目前仍知之甚少。我们发现，小鼠在以3戈瑞/分钟的剂量率接受10分钟的颅脑照射3个月后出现认知障碍。此外，我们观察到海马CA1锥体神经元的动作电位发放和兴奋性突触输入显著减少，而抑制性输入则大幅增强。与这种电生理适应性变化相对应，我们发现突触可塑性标记物VGLUT1的表达降低，而VGAT的表达增加。此外，在受照射的小鼠中，海马的长时程增强效应减弱，GluR1的表达受到抑制。这些研究结果表明，辐射会损害海马CA1锥体神经元的内在兴奋性和突触可塑性。