Microglia induce auditory dysfunction after status epilepticus in mice
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Araki, Tasuku
[1
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Hiragi, Toshimitsu
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Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
Hiragi, Toshimitsu
[1
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Kuga, Nahoko
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Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Sendai, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
Kuga, Nahoko
[1
,2
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Luo, Cong
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Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
Luo, Cong
[1
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Andoh, Megumi
[1
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Sugao, Kohtaroh
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Sumitomo Pharm Co Ltd, Osaka, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
Sugao, Kohtaroh
[3
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Nagata, Hidetaka
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Sumitomo Pharm Co Ltd, Osaka, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
Nagata, Hidetaka
[3
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Sasaki, Takuya
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Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Sendai, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
Sasaki, Takuya
[1
,2
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Ikegaya, Yuji
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Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
Univ Tokyo, Inst AI & Beyond, Tokyo, Japan
Natl Inst Informat & Commun Technol, Ctr Informat & Neural Networks, Osaka, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
Ikegaya, Yuji
[1
,4
,5
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Koyama, Ryuta
[1
,4
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[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Chem Pharmacol, Tokyo, Japan
[2] Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Sendai, Japan
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
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Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Niquet, Jerome
Lopez-Meraz, Maria-Leonor
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机构:Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Lopez-Meraz, Maria-Leonor
Wasterlain, Claude G.
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机构:Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA