Microglia induce auditory dysfunction after status epilepticus in mice

被引:0
作者
Araki, Tasuku [1 ]
Hiragi, Toshimitsu [1 ]
Kuga, Nahoko [1 ,2 ]
Luo, Cong [1 ]
Andoh, Megumi [1 ]
Sugao, Kohtaroh [3 ]
Nagata, Hidetaka [3 ]
Sasaki, Takuya [1 ,2 ]
Ikegaya, Yuji [1 ,4 ,5 ]
Koyama, Ryuta [1 ,4 ]
机构
[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
[2] Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Sendai, Japan
[3] Sumitomo Pharm Co Ltd, Osaka, Japan
[4] Univ Tokyo, Inst AI & Beyond, Tokyo, Japan
[5] Natl Inst Informat & Commun Technol, Ctr Informat & Neural Networks, Osaka, Japan
基金
日本科学技术振兴机构; 日本学术振兴会;
关键词
auditory dysfunction; epilepsy; medial geniculate body; microglia; status epilepticus; synaptic E/I balance; synaptic stripping; INDUCED SEIZURES; SYNCHRONIZATION; MODULATION; PHYSIOLOGY; RECEPTORS; THALAMUS; EPILEPSY; MODEL; BODY;
D O I
10.1002/glia.24472
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Auditory dysfunction and increased neuronal activity in the auditory pathways have been reported in patients with temporal lobe epilepsy, but the cellular mechanisms involved are unknown. Here, we report that microglia play a role in the disinhibition of auditory pathways after status epilepticus in mice. We found that neuronal activity in the auditory pathways, including the primary auditory cortex and the medial geniculate body (MGB), was increased and auditory discrimination was impaired after status epilepticus. We further demonstrated that microglia reduced inhibitory synapses on MGB relay neurons over an 8-week period after status epilepticus, resulting in auditory pathway hyperactivity. In addition, we found that local removal of microglia from the MGB attenuated the increase in c-Fos+ relay neurons and improved auditory discrimination. These findings reveal that thalamic microglia are involved in auditory dysfunction in epilepsy. In mice after status epilepticus, neuronal activity in the medial geniculate body (MGB) increased in parallel with an impairment in auditory discrimination.MGB microglia depletion suppressed neural hyperactivity and improved auditory discrimination.image
引用
收藏
页码:274 / 288
页数:15
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