Chronic early life lead (Pb²⁺) exposure alters presynaptic vesicle pools in hippocampal synapses

Lead (Pb²⁺) exposure has been shown to impair presynaptic neurotransmitter release in both in vivo and in vitro model systems. The mechanism by which Pb²⁺ impairs neurotransmitter release has not been fully elucidated. In previous work, we have shown that Pb²⁺ exposure inhibits vesicular release and reduces the number of fast-releasing sites in cultured hippocampal neurons. We have also shown that Pb²⁺ exposure inhibits vesicular release and alters the distribution of presynaptic vesicles in Shaffer Collateral - CA1 synapses of rodents chronically exposed to Pb²⁺ during development.

In the present study, we used transmission electron microscopy to examine presynaptic vesicle pools in Mossy Fiber-CA3 synapses and in Perforant Path-Dentate Gyrus synapses of rats to determine if in vivo Pb²⁺ exposure altered presynaptic vesicle distribution in these hippocampal regions. Data were analyzed using T-test for each experimental endpoint.

We found that Pb²⁺ exposure significantly reduced the number of vesicles in the readily releasable pool and recycling pool in Mossy Fiber-CA3 terminals. In both Mossy Fiber-CA3 terminals and in Perforant Path-Dentate Gyrus terminals, Pb²⁺ exposure significantly increased vesicle nearest neighbor distance in all vesicular pools (Rapidly Releasable, Recycling and Resting). We also found a reduction in the size of the postsynaptic densities of CA3 dendrites in the Pb²⁺ exposed group.

In our previous work, we have demonstrated that Pb²⁺ exposure impairs vesicular release in Shaffer Collateral - CA1 terminals of the hippocampus and that the number of docked vesicles in the presynaptic active zone was reduced. Our current data shows that Pb²⁺ exposure reduces the number of vesicles that are in proximity to release sites in Mossy Fiber- CA3 terminals. Furthermore, Pb²⁺ exposure causes presynaptic vesicles to be further from one another, in both Mossy Fiber- CA3 terminals and in Perforant Pathway - Dentate Gyrus terminals, which may interfere with vesicle movement and release. Our findings provide a novel in vivo mechanism by which Pb²⁺ exposure impairs vesicle dynamics and release in the hippocampus.