The influence of developmental period of lead exposure on long-term potentiation in the adult rat dentate gyrus in vivo.
Previous work has demonstrated an increase in the threshold for induction of long-term potentiation (LTP) in the dentate gyrus of animals chronically exposed to lead (Pb) from birth (Gilbert et al., 1996). The present study sought to extend these findings by evaluating the developmental periods critical for Pb-induced impairment of LTP. Rats were exposed to Pb through maternal milk and/or the drinking water over different developmental intervals: 1) beginning just prior to birth and continuing throughout life (PL); 2) beginning just prior to birth and terminating at weaning (PW); or 3) continuously from the early post-weaning period throughout life (WL). Pregnant dams received 0.2% Pb-acetate in the drinking water on gestational day (GD)16, with male offspring switched to the same solution (PL group) or tap water (PW group) at weaning on postnatal day (PND)21. Postweaning exposure began on PND30 and continued throughout life. As adults (PND130-210), field potentials evoked by perforant path stimulation were recorded in the dentate gyrus under urethane anesthesia, and an ascending series of stimulus trains was administered to induce LTP and to determine its threshold. The magnitude of population spike (PS) LTP was reduced relative to controls in animals exposed throughout life (PL) and in animals exposed after weaning (WL). No impairment in PS LTP was evident in animals removed from Pb at weaning and tested as adults (PW). Similarly, thresholds for induction of PS LTP were elevated relative to controls in the PL and WL groups, but were not affected by Pb exposure limited to the lactational period (PW). Reductions in the magnitude of LTP of the EPSP slope were evident in posttrain I/O functions in all Pb-exposed groups, including the PW group. An elevated LTP threshold was evident in the EPSP slope measure in the continuously exposed group (PL) only. Thus Pb exposure restricted to the lactational period appeared less disruptive to adult LTP in the dentate gyrus than continuous exposure beginning around birth or weaning. However, EPSP slope LTP was impaired in animals exposed to Pb for as little as 30 days in the early postnatal period. An attenuated ability to support neuroplastic change in synaptic function may contribute to cognitive deficits associated with Pb-induced toxicity.
Gilbert
M E
ME
National Research Council and Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. gilbert.mary@epamail.epa.gov
Mack
C M
CM
Lasley
S M
SM
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D000833:Animals, Suckling / Q000502:physiology; D001921:Brain / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans
D007854:Lead