RT Journal Article
SR Electronic
T1 Neuregulin-1 Reverses Long-Term Potentiation at CA1 Hippocampal Synapses
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9378
OP 9383
DO 10.1523/JNEUROSCI.2100-05.2005
VO 25
IS 41
A1 Oh-Bin Kwon
A1 Marines Longart
A1 Detlef Vullhorst
A1 Dax A. Hoffman
A1 Andres Buonanno
YR 2005
UL http://www.jneurosci.org/content/25/41/9378.abstract
AB 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-1β 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-1β 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-1β 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-1β 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.