Lead blocks LTP by an action not at NMDA receptors.
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.
Hori
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N
Wadsworth Center for Laboratories and Research, New York State Department of Health and School of Public Health, Albany 12201-0509.
Büsselberg
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D
Matthews
M R
MR
Parsons
P J
PJ
Carpenter
D O
DO
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology*; D009833:Olfactory Pathways / Q000187:drug effects* / Q000502:physiology; D009994:Osmolar Concentration; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D007854:Lead; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid