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ASSESSING HIPPOCAMPAL CHANGES INDICATIVE OF NEUROTOXIC EFFECTS.
Citation:
Gilbert, M. E. ASSESSING HIPPOCAMPAL CHANGES INDICATIVE OF NEUROTOXIC EFFECTS. Presented at Society of Toxicology -- Inv. Workshop Pres, Baltimore, MD, 3/21-25/03.
Description:
Subtle changes in cognitive function are often the earliest indication of neurotoxic effects in humans. The hippocampus is a large forebrain structure subserving specific kinds of information encoding and consolidation in humans and other animals. Because of it laminar structure, it is ideally suited for neurophysiological assessment and it is readily accessible for both in vitro and in vivo examination. The homogeneity of the neural populations within each cell body layer results in large field potential recordings that faithfully reflect intracellular current flow. As such, these field potentials can be directly translated to activity at the cellular level. Hippocampal field potentials also display a high degree of synaptic plasticity and a well accepted synaptic model of memory, long-term potentiation, has been characterized in this structure. However, toxicological assessments of hippocampal function using this approach are relatively sparse, and in vitro assessments using slices or cultures are more prevalent than in vivo investigations. The bulk of neurotoxicological investigations in vivo have examined the long-term consequences of developmental exposure, although acute effects of chemical exposures have also been reported for pyrethroid, formamadine, and organochlorine pesticides. Developmental insults include pre and/or postnatal exposure to ethanol, carbon monoxide, lead, antimitotic agents, and thyroid disrupting compounds. The majority of these studies have demonstrated altered hippocampal synaptic function that in all likelihood represents permanent alterations in cell communication following early developmental insult. These perturbations are often present in the absence of overt pathological changes in structure and in the absence of behavioral impairments based on standard learning and memory assessments. Abstract does not necessarily reflect USEPA policy.