Two components of long-term depression are impaired by chronic lead exposure in area CA1 and dentate gyrus of rat hippocampus in vitro

Previous studies have demonstrated that low-level lead exposure can impair the induction of long-term depression (LTD) in area CA1 and dentate gyrus (DG) of rat hippocampus in vitro and in vivo. The induction of LTD in area CAI and DG has been shown to associate with N-methyl-D-aspartate receptors (NMDARs) and voltage-gated calcium channel (VGCC). In this study, the relative contributions of NMDARs-dependent and VGCC-dependent components in the induction of LTD in the hippocampus and the impairments of these two components of LTD by chronic low-level lead exposure were investigated. 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 area CA1 and DG before and after two 15-min trains of 1-Hz Iow-frequency stimulation (LFS) (2x900 pulses). In area CA1, the amplitude of NMDARs-dependent LTD (NMDA-LTD), in the presence of 10 muM nimodipine (a blocker of L-type Ca2+ channels), was 80.05 +/- 2.54% (n=8) and 94.58 +/- 10.57% (n=8) in the control and lead-exposed rats, respectively. The amplitude of VGCC-dependent LTD (VGCC LTD), in the presence of 50 muM (-)-2-amino-5-phosphonopentanoic acid (AP5), was 80.36 +/- 3.08% (n = 10) and 93.91 +/- 7.85% (n = 10) in the control and lead-exposed rats, respectively. Ln area DG the amplitude of NMDA-LTD, with both 50 muM Ni2+ (a blocker of T-type Ca2+ channels) and 10 muM nimodipine present, in the control rats (79.97 +/- 4.30%, n=8) was significantly larger than that in the lead-exposed rats (91.24 +/- 11.08%, n=10, P < 0.001). The amplitude of VGCC-LTD, with 50 <mu>M AP5 present, was significantly larger in the control rats (70.80 +/- 3.64%, n = 9) than that in the lead - exposed rats (87.60 +/- 9.00%, n = 10, P < 0.001). The results suggested that chronic lead exposure affected two components of LTD induction in area CA1 and DG. Furthermore, the impairment of two components by lead exposure might be similar in area CAI, while the impairment of VGCC-LTD might be more serious in DG of hippocampus. (C) 2000 Elsevier Science Inc. All rights reserved.