Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 41, Pages 9378-9383Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2100-05.2005
Keywords
neuregulin; depotentiation; ErbB receptor; LTP; LTD; schizophrenia; superecliptic GFP
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Funding
- Intramural NIH HHS [Z99 HD999999] Funding Source: Medline
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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-1 beta 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-1 beta 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-1 beta 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-1 beta 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.
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