Lead blocks LTP by an action not at NMDA receptors

N. Hori, Dietrich Busselberg, M. R. Matthews, P. J. Parsons, D. O. Carpenter

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Exposure of children to low levels of lead results in a reduction in cognitive ability and a series of behavioral deficits. We have studied the effects of PbCl2 on longterm potentiation (LTP), the best available electrophysiologic model of learning and memory, in a rat piriform cortex brain slice preparation in order to test the hypothesis that lead neurotoxicity is a result of actions on LTP. With changes in the composition of the Krebs-Ringer solution normally used in brain slices, it is possible to keep the Pb2+ in solution at concentrations up to 10 μM. In this concentration range, Pb2+ has no effect on the synaptic response elicited in piriform cortex pyramidal neurons upon stimulation of the lateral olfactory tract. We find that Pb2+ blocks LTP by about 75% at 5 μM and completely at 10 μM. At these concentrations, Pb2+ has no effect on posttetanic potentiation. Since it has been reported that Pb2+ blocks N-methyl-D-aspartate (NMDA) responses, and NMDA blockade is known at many sites to block LTP, we studied the effects of Pb2+ on NMDA responses. In the concentration range studied there was no effect of Pb2+ on NMDA responses. The mechanism whereby Pb2+ blocks LTP remains to be determined. While the concentration of Pb2+ found to block LTP in these studies is high relative to concentrations of Pb2+ in blood that are associated with causing cognitive and behavioral effects in children, the sensitivity to Pb2+ may be greater in young animals.

Original languageEnglish
Pages (from-to)192-197
Number of pages6
JournalExperimental Neurology
Issue number2
Publication statusPublished - 1993
Externally publishedYes


ASJC Scopus subject areas

  • Neuroscience(all)
  • Neurology

Cite this

Hori, N., Busselberg, D., Matthews, M. R., Parsons, P. J., & Carpenter, D. O. (1993). Lead blocks LTP by an action not at NMDA receptors. Experimental Neurology, 119(2), 192-197. https://doi.org/10.1006/exnr.1993.1020