ErbB4 is a suppressor of long-term potentiation in the adult hippocampus

被引:66
作者
Pitcher, Graham M. [1 ,2 ]
Beggs, Simon [1 ]
Woo, Ran-Sook [3 ,4 ]
Mei, Lin [3 ,4 ]
Salter, Michael W. [1 ,2 ]
机构
[1] Hosp Sick Children, Program Neurosci & Mental Hlth, Dept Phys, Toronto, ON M5G 1X8, Canada
[2] Univ Toronto, Dept Phys, Toronto, ON, Canada
[3] Inst Mol Med & Genet, Med Coll Georgia, Dept Neurol, Augusta, GA USA
[4] Inst Mol Med & Genet, Med Coll Georgia, Program Dev Neurobiol, Augusta, GA USA
基金
加拿大健康研究院;
关键词
ErbB4; long-term potentiation; neuregulin; paired-pulse facilitation; Schaffer collateral CAI synapses; synaptic plasticity; theta burst stimulation; transgenic mouse;
D O I
10.1097/WNR.0b013e3282f3da10
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
ErbB4 has emerged as a leading susceptibility gene for schizophrenia but the function of the ErbB4 receptor in the adult brain is unknown. Here, we show in the adult hippocampus that long-term potentiation (LTP) of transmission at Schaffer collateral CAI synapses was markedly enhanced in mutant mice lacking ErbB4. Concordantly, LTP was enhanced by acutely blocking ErbB4 in wild-type animals, indicating that ErbB4 activity constitutively suppresses LTR Moreover, increasing ErbB4 signaling further suppressed LTP. By contrast, altering ErbB4 activity did not affect basal synaptic transmission or short-term facilitation. Our findings suggest that cognitive deficits in schizophrenia may be a consequence of hyperfunction of ErbB4 signaling leading to suppressed glutamatergic synaptic plasticity, thus opening new approaches for the treatment of this disorder.
引用
收藏
页码:139 / 143
页数:5
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