LONG-TERM POTENTIATION IN THE PIRIFORM CORTEX IS BLOCKED BY LEAD

1. Long-term potentiation (LTP) is a prolonged increase in synaptic ef ficacy that is triggered by a brief tetanic stimulation at certain cen tral synapses. LTP is one of the best available model systems availabl e to the neurophysiologist of neuronal plasticity such as that underly ing learning and memory. 2. We have studied the susceptibility of LTP to blockade by lead as a test of the hypothesis that the negative effe ct of lead on intelligence in children may result from interference wi th this process. LTP was studied in slices of rat piriform cortex. At this site, as in many other central synapses, LTP requires activation of postsynaptic N-methyl-D-aspartate (NMDA) receptors, and we investig ated whether lead actions, if any, were mediated via effects on NMDA-a ctivation ion channels or, alternatively, at voltage-activated calcium channels. 3. We find that lead blocks LTP at low micromolar concentra tions. However, concentrations of lead that totally block LTP had no a pparent effect on either NMDA-activated responses or presynaptic calci um channels, as monitored by transmitter release from presynaptic term inals. 4. While the mechanism of lead blockade of LTP remains to be de termined, these observations are consistent with the hypothesis that t he cognitive effects of lead neurotoxicity may result from effects on LTP.