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.