title: Chronic developmental lead exposure increases the threshold for long-term potentiation in rat dentate gyrus in vivo.
abstract: Chronic developmental lead (Pb) exposure has been long associated with cognitive dysfunction in children and animals. In an attempt to more directly relate the behavioral observations of impaired cognitive ability to Pb-induced effects on neuronal activity, we utilized the long-term potentiation (LTP) model of neural plasticity to assess synaptic function. Male rats were chronically exposed to 0.2% Pb(2+)-acetate through the drinking water of the pregnant dam, and directly through their own water supply at weaning. As adults, field potentials evoked by perforant path stimulation were recorded in the dentate gyrus under urethane anesthesia. LTP threshold was determined by applying a series of stimulus trains of increasing intensities. Baseline testing of dentate gyrus field potentials indicated that input/output functions, maximal response amplitudes, and threshold currents required to evoke a population spike (PS) did not differ for control and Pb-exposed animals. Despite similarities in baseline synaptic transmission, Pb-exposed animals required a higher train intensity to evoke LTP than controls. With maximal train stimulation, however, control and Pb animals exhibited comparable levels of potentiation. These findings suggest that the mechanisms of LTP induction are preferentially impaired by Pb exposure. Although baseline synaptic transmission was not altered in Pb-exposed animals, decreases in glutamate release following high K+ perfusion and reductions in paired pulse facilitation have been reported in the intact animal. Pb-induced reductions in calcium influx through voltage-sensitive or N-methyl-D-aspartate (NMDA) receptor-dependent channels may mediate increases in LTP threshold. It is possible that the threshold changes in the induction of LTP reported here contribute to cognitive impairments associated with Pb exposure.
authors.affiliation: National Research Council, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. gilbert@herl45.herl.epa.gov
authors.forename: M E
authors.initials: ME
authors.lastname: Gilbert
authors.forename: C M
authors.initials: CM
authors.lastname: Mack
authors.forename: S M
authors.initials: SM
authors.lastname: Lasley
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002648:Child; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D005071:Evoked Potentials; D005260:Female; D006801:Humans; D007855:Lead Poisoning / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D012016:Reference Values; D009435:Synaptic Transmission
chemical_list: D009942:Organometallic Compounds; C008261:lead acetate