CHRONIC LEAD-EXPOSURE ACCELERATES DECAY OF LONG-TERM POTENTIATION IN RAT DENTATE GYRUS IN-VIVO

Long-term potentiation (LTP) is a model of synaptic plasticity believe d to encompass the underlying neurobiological mechanisms that support memory function. Chronic developmental lead (Pb) exposure is known to be associated with cognitive dysfunction in children and animals. Disr uption of the induction of long-term potentiation (LTP) has been repor ted in the hippocampus following chronic exposure to environmentally r elevant levels of Pb in rats. Under urethane anesthesia, we have previ ously observed Ph-induced increases in the threshold for LTP induction . With higher train intensities, LTP was induced and no declines in th e amplitude of responses within a 60-min posttrain period were evident . The present study was designed to assess the effects of Pb on the mo re enduring forms of LTP in the dentate gyrus of the conscious rat. Be ginning in the late gestational period, rats were chronically exposed to 0.2% Pb2+-acetate through the drinking water of the pregnant dam, a nd directly through their own water supply at weaning. As adults, elec trodes were permanently implanted in male offspring and field potentia ls evoked by perforant path stimulation were recorded from the dentate gyrus over several weeks. LTP was induced by delivering theta-burst p atterned stimulation at a maximal stimulus intensity through the perfo rant path electrode, and input/output (I/O) functions were monitored f or 1 month. Population spike (PS) amplitude was increased maximally 1 h after train delivery. The time constant of decay (tau) calculated fr om pooled data for each group yielded declines in PS amplitude by 63% in 17.4 days in controls and 13.4 days in Pb-exposed animals. Quantita tive estimates of decay in individual animals were achieved in two way s: (1) by calculating difference scores in I/O functions from the maxi mal LTP at 1 h, and (2) by interpolating day to decay by 63% from decl ines from maximal LTP. The interpolated values were used to compare th e incidence of animals showing decay of 63% within 1 week posttrain, B oth analyses revealed a more accelerated rate of decay of LTP in anima ls developmentally exposed to Pb relative to controls. Endurance of po tentiated responses for days to weeks is believed to be supported by s tructural modifications and synaptic growth. The reported effects of P b on growth-related processes may thus contribute to a reduced persist ence of LTP and the resulting cognitive deficits engendered by develop mental ph exposure. (C) 1998 Elsevier Science B.V.