The effects of chronic lead exposure on long-term depression in area CA1 and dentate gyrus of rat hippocampus in vitro

Abstract

Long-term potentiation (LTP) and long-term depression (LTD), two forms of synaptic plasticity, are believed to underlie the mechanisms of learning and memory. Previous studies have demonstrated that low-level lead exposure can impair the induction and maintenance of LTP in vivo and in vitro. The present study was carried out to investigate whether the low-level lead exposure affected the induction and maintenance of LTD. Neonatal Wistar rats were exposed to lead from parturition to weaning via milk of dams drinking 0.2% lead acetate solution. Field excitatory postsynaptic potentials (EPSPs) were recorded in hippocampal slices in adult rats (50–65 days) to study the alterations of LTD in area CA1 and dentate gyrus (DG) of hippocampus following chronic lead exposure. The input–output (I/O) curves before conditioning in both areas showed no evident alterations in basic synaptic transmission between the control and lead exposure groups. In area CA1, the mean amplitude of EPSP slope in control rats (61±11%, n=15) decreased significantly greater than that in lead-exposed rats (78±8%, n=8, P<0.05) following low frequency stimulation (LFS, 1 Hz, 15 min), which lasted at least 45 min. In area DG, with application of the same LFS, the LTD was induced in control rats (72±22%, n=8), while the LFS failed to induce LTD in lead-exposed rats (100±26%, n=8). These results showed that chronic lead exposure affected the induction of LTD in both area CA1 and DG. The effect of lead on synaptic plasticity in area CA1 was also investigated. The alteration of the amplitude of LTP in hippocampal slices caused by lead was reexamined in order to compare with that on LTD (control: 189±23, n=5; lead-exposed: 122±12, n=10). The result demonstrated that low-level lead exposure could reduce the range of synaptic plasticity, which might underlie the dysfunction of learning and memory caused by chronic lead exposure.