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

Min Yi Wu, Wen Jun Zou, Pei Yu, Yuhua Yang, Shao Jian Li, Qiang Liu, Jiatian Xie, Si Qi Chen, Wei Jye Lin, Yamei Tang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2253-2259
Number of pages7
JournalNeural Regeneration Research
Volume17
Issue number10
DOIs
StatePublished - Oct 2022
Externally publishedYes

Keywords

  • GABA-mediated hyperfunction
  • GluR
  • intrinsic excitability
  • long-term potentiation
  • radiation-induced cognitive impairment
  • spontaneous excitatory postsynaptic currents
  • spontaneous inhibitory postsynaptic currents
  • synaptic plasticity
  • type I vesicular glutamate transporter
  • vesicular GABA transporter
  • whole-cell patch clamp recording

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