Neuregulin-1 reverses long-term potentiation at CA1 hippocampal synapses.
Neuregulin-1 (NRG-1) has been identified genetically as a schizophrenia susceptibility gene, but its function in the adult brain is unknown. Here, we show that NRG-1beta does not affect basal synaptic transmission but reverses long-term potentiation (LTP) at hippocampal Schaffer collateral-->CA1 synapses in an activity- and time-dependent manner. Depotentiation by NRG-1beta is blocked by two structurally distinct and selective ErbB receptor tyrosine kinase inhibitors. Moreover, ErbB receptor inhibition increases LTP at potentiated synapses and blocks LTP reversal by theta-pulse stimuli. NRG-1beta selectively reduces AMPA, not NMDA, receptor EPSCs and has no effect on paired-pulse facilitation ratios. Live imaging of hippocampal neurons transfected with receptors fused to superecliptic green fluorescent protein, as well as quantitative analysis of native receptors, show that NRG-1beta stimulates the internalization of surface glutamate receptor 1-containing AMPA receptors. This novel regulation of LTP by NRG-1 has important implications for the modulation of synaptic homeostasis and schizophrenia.
Kwon
Oh-Bin
OB
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-3714, USA.
Longart
Marines
M
Vullhorst
Detlef
D
Hoffman
Dax A
DA
Buonanno
Andres
A
D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020890:Neuregulin-1 / Q000494:pharmacology* / Q000502:physiology*; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D020890:Neuregulin-1