Suppression of long-term potentiation in hippocampal slices by copper

Hippocampus. 1997;7(6):666-9. doi: 10.1002/(SICI)1098-1063(1997)7:6<666::AID-HIPO8>3.0.CO;2-C.


Cu(2+)-ions are known to interfere with gamma-aminobutyric acid (GABA)- and glutamate-operated ion channels from experiments with isolated neurons. Such actions are likely involved in the pathophysiology of Wilson's disease. We have now studied the effects of Cu2+ in the CA1 region of hippocampal slices. Field excitatory postsynaptic potential (EPSP) slopes in the CA1 region were unaffected by 1 microM Cu2+ but were depressed by 10 microM (to 85%) and 100 microM (to 50%). A paired-pulse test revealed no difference in facilitation in the presence or absence of Cu2+, indicating a postsynaptic action. A late component of intracellularly registered EPSPs in Mg(2+)-free solution was also reduced by Cu2+. The N-methyl-D-aspartate (NMDA) component of the field EPSP, isolated by adding CNQX and bicuculline in Mg(2+)-free solution, was reduced to 69% of control by 1 microM and to 50% of control by 10 microM Cu2+. Long-term potentiation, evoked by 3 x 50 pulses at 100 Hz, 20 s interval amounted to 132 +/- 11% 90 min after tetanization under control conditions but was absent in the presence of 1 microM Cu2+ in the bath. Thus low concentrations of copper can selectively reduce NMDA-mediated potentials and synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Copper / pharmacology*
  • Depression, Chemical
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / drug effects*
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Magnesium / physiology
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism


  • Receptors, N-Methyl-D-Aspartate
  • Copper
  • Magnesium