title: Long-term consequences of developmental exposure to lead or polychlorinated biphenyls: Synaptic transmission and plasticity in the rodent CNS.
abstract: Exposure to lead (Pb) or polychlorinated biphenyls (PCBs) during early development has been associated with deficits in cognitive function in children (Pediatrics 87 (1991) 219; N. Engl. J. Med. 335 (1996) 783). These effects persist in the child long after exposure has ceased and body burdens have diminished. Despite intensive research, no consensus on the mechanisms of neurotoxicity of these chemicals has resulted. As the primary neurotoxic action of these agents is to impair cognitive ability, a number of laboratories have examined and reported on the detrimental the effects of Pb or PCBs on hippocampal synaptic transmission and long-term potentiation (LTP) in animals exposed during the perinatal period. Use-dependent synaptic plasticity, of which hippocampal LTP is the primary model system, is a fundamental property of neuronal function. In forebrain structures such as amygdala and hippocampus, LTP and related processes are purported to represent a physiological substrate for memory. During brain ontogeny, this type of plasticity guides the establishment and maintenance of synaptic connections in cortical structures based on sensory input. We postulate that the actions of PCBs and Pb in the developing nervous system perturb activity-dependent plasticity and promote organizational changes in brain. Aberrant connectivity derived from perturbations in activity-dependent plasticity during development may manifest as impaired LTP and cognitive ability in the adult organism.
authors.affiliation: Neurotoxicology Division (MD 74B), National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Gilbert
authors.forename: S M
authors.initials: SM
authors.lastname: Lasley