TY - JOUR
T1 - The Neuregulin-1 Receptor ErbB4 Controls Glutamatergic Synapse Maturation and Plasticity
AU - Li, Bo
AU - Woo, Ran Sook
AU - Mei, Lin
AU - Malinow, Roberto
N1 - Funding Information:
This work was supported by the National Institutes of Health (R.M., L.M.), MDA (L.M.), and the Canadian Institute of Health Research (B.L.; Postdoctoral Fellowship). We thank Nancy Dawkins for preparation of hippocampal slice cultures; Yu Fu for making the NRG1 expressing constructs in Sindbis vector; Dr. Charles D. Kopec for programming image analysis software; Barry Burbach, Peter O'Brien, and Dr. Svoboda for assistance on the microscope; Drs. Tsien, Miesenbock, Hannon, and Nawa for supplying reagents; Dr. S. Muthuswamy and members of the Malinow lab for helpful discussions.
PY - 2007/5/24
Y1 - 2007/5/24
N2 - Neuregulin-1 (NRG1) signaling participates in numerous neurodevelopmental processes. Through linkage analysis, nrg1 has been associated with schizophrenia, although its pathophysiological role is not understood. The prevailing models of schizophrenia invoke hypofunction of the glutamatergic synapse and defects in early development of hippocampal-cortical circuitry. Here, we show that the erbB4 receptor, as a postsynaptic target of NRG1, plays a key role in activity-dependent maturation and plasticity of excitatory synaptic structure and function. Synaptic activity leads to the activation and recruitment of erbB4 into the synapse. Overexpressed erbB4 selectively enhances AMPA synaptic currents and increases dendritic spine size. Preventing NRG1/erbB4 signaling destabilizes synaptic AMPA receptors and leads to loss of synaptic NMDA currents and spines. Our results indicate that normal activity-driven glutamatergic synapse development is impaired by genetic deficits in NRG1/erbB4 signaling leading to glutamatergic hypofunction. These findings link proposed effectors in schizophrenia: NRG1/erbB4 signaling perturbation, neurodevelopmental deficit, and glutamatergic hypofunction.
AB - Neuregulin-1 (NRG1) signaling participates in numerous neurodevelopmental processes. Through linkage analysis, nrg1 has been associated with schizophrenia, although its pathophysiological role is not understood. The prevailing models of schizophrenia invoke hypofunction of the glutamatergic synapse and defects in early development of hippocampal-cortical circuitry. Here, we show that the erbB4 receptor, as a postsynaptic target of NRG1, plays a key role in activity-dependent maturation and plasticity of excitatory synaptic structure and function. Synaptic activity leads to the activation and recruitment of erbB4 into the synapse. Overexpressed erbB4 selectively enhances AMPA synaptic currents and increases dendritic spine size. Preventing NRG1/erbB4 signaling destabilizes synaptic AMPA receptors and leads to loss of synaptic NMDA currents and spines. Our results indicate that normal activity-driven glutamatergic synapse development is impaired by genetic deficits in NRG1/erbB4 signaling leading to glutamatergic hypofunction. These findings link proposed effectors in schizophrenia: NRG1/erbB4 signaling perturbation, neurodevelopmental deficit, and glutamatergic hypofunction.
KW - CELLBIO
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U2 - 10.1016/j.neuron.2007.03.028
DO - 10.1016/j.neuron.2007.03.028
M3 - Article
C2 - 17521571
AN - SCOPUS:34248531426
SN - 0896-6273
VL - 54
SP - 583
EP - 597
JO - Neuron
JF - Neuron
IS - 4
ER -