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.

Automated summary

Radiation therapy for head and neck tumors can result in cognitive impairments, which are related to abnormal hippocampal function. However, the long-term effects of radiation on the electrophysiological adaptation of hippocampal neurons are not well understood. This study found that mice exhibited cognitive impairment three months after cranial irradiation, and there was a reduction in spike firing and excitatory synaptic input, as well as an increase in inhibitory inputs in hippocampal CA1 pyramidal neurons. These changes were associated with altered expression of synaptic plasticity markers. Overall, radiation can impair intrinsic excitability and synaptic plasticity in hippocampal neurons.