PRESYNAPTIC GLUTAMATERGIC FUNCTION IN DENTATE GYRUS IN-VIVO IS DIMINISHED BY CHRONIC EXPOSURE TO INORGANIC LEAD

Reductions in membrane Ca2+ channel currents and depolarization-evoked neurotransmitter release have been repeatedly observed as a result of acute exposure to Pb2+. This study was performed to determine whether hippocampal glutamate and GABA release are impaired in intact animals chronically exposed to lead (Pb). As paired-pulse facilitation in the hippocampus is primarily mediated by an enhancement of glutamate rele ase, this neurophysiological measure was also assessed in the dentate gyrus of Pb-exposed animals. Pregnant dams received 0.2% Pb acetate in the drinking water at parturition, and male offspring were weaned to the same solution as that given their dams. Control animals were maint ained on distilled water. As adults, animals had intracerebral dialysi s probes inserted through guide cannulae implanted 2-4 days previously and the hippocampal CA1-dentate area was perfused with modified Ringe r's solution. Transmitter release was induced by perfusion with 150 mM K+ with half the animals in each group tested with Ca2+ present in th e perfusate (total release) and the other half with Ca2+ absent (Ca2+- independent release). K+-stimulated total glutamate release was reduce d in Pb-exposed animals relative to controls. No group differences wer e observed under Ca2+-free conditions, indicating that Ca2+-dependent glutamate release was decreased in exposed rats. In contrast no group differences in K+-stimulated total GABA release were evident, whereas an augmentation in GABA release under Ca2+-free conditions was reveale d in Pb-exposed animals. The effects of exposure on the Ca2+-dependent components of release are consistent with in vitro evidence indicatin g an inhibitory action of Pb2+ at voltage-sensitive Ca2+ channels. A s eparate group of animals was prepared under urethane anesthesia with s timulating and recording electrodes placed in the perforant path and d entate gyrus, respectively. Pairs of stimulus purses were delivered at interpulse intervals (IPI) of 10-250 ms. Pb exposure induced an incre ase in paired-pulse depression at the 20 ms IPI and reduced paired-pul se facilitation at the 30 ms IPI. Decreases in paired-pulse facilitati on could not be attributed to the reported effects of Pb2+ on N-methyl -D-aspartate (NMDA) receptors as MK-801 (1.0 mg/kg, s.c.) administrati on produced an opposing pattern of effects on paired-pulse measures. T he Pb-induced suppression of paired-pulse facilitation is consistent w ith exposure-related decreases in total glutamate release. The impact of these effects of Pb exposure on hippocampal glutamatergic transmiss ion may contribute to the reported effects of Pb on other forms of syn aptic plasticity including long-term potentiation, a model of learning and memory.