Lead blocks LTP by an action not at NMDA receptors. Academic Article uri icon

Overview

abstract

  • 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 long-term 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 microM. 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 microM and completely at 10 microM. 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.

publication date

  • February 1, 1993

Research

keywords

  • Lead
  • Olfactory Pathways
  • Receptors, N-Methyl-D-Aspartate

Identity

Scopus Document Identifier

  • 0027241824

Digital Object Identifier (DOI)

  • 10.1006/exnr.1993.1020

PubMed ID

  • 8432359

Additional Document Info

volume

  • 119

issue

  • 2