ErbB4 is a suppressor of long-term potentiation in the adult hippocampus.
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 CA1 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 LTP. 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.
Pitcher
Graham M
GM
Program in Neurosciences & Mental Health, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. graham.pitcher@utoronto.ca
Beggs
Simon
S
Woo
Ran-Sook
RS
Mei
Lin
L
Salter
Michael W
MW
D000818:Animals; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D066247:Receptor, ErbB-4; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000235:genetics; D013826:Theta Rhythm
D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4