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PERSISTENT IMPAIRMENTS IN SHORT-TERM BUT ENHANCED LONG-TERM SYNAPTIC PLASTICITY IN HIPPOCAMPAL AREA CA1 FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM.
Citation:
Sui, L., W L. Anderson, AND M. E. Gilbert. PERSISTENT IMPAIRMENTS IN SHORT-TERM BUT ENHANCED LONG-TERM SYNAPTIC PLASTICITY IN HIPPOCAMPAL AREA CA1 FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM. Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, UT, March 9-13, 2003.
Description:
Thyroid hormones (TH) are critical for nervous system development. Deficiency of TH during development impair performance on tasks of learning and memory that rely upon the hippocampus, but the mechanism underlying this impairment is not well understood. The present study was designed to identify hypothyroid-induced changes in hippocampal function using neurophysiological assessments in area CA1 of hippocampal slices. Hypothyroidism was induced by administration of 3 or 10ppm propylthiouracil (PTU) to pregnant and lactating dams via the drinking water from GD6-PN30. Synaptic transmission and plasticity using the long-term potentiation (LTP) model were assessed in area CA1 of hippocampal slices from treated offspring. Input/output and paired-pulse functions were collected to assess the integrity of synaptic transmission at PN85-95. Baseline synaptic transmission was not altered in PTU-exposed animals. However, significant dose-dependent reductions in paired-pulse facilitation of the EPSP were observed, indicative of perturbations in presynaptic transmitter release function. An increase in magnitude of LTP of the PS and increased phosphorylation of MAPK/ERK as a function of LTP induction were also observed in the high dose group. Neurophysiological assessments in the preweaning period and in adults in a different hippocampal subregion (i.e., dentate gyrus) demonstrate a different pattern of effects and more profound deficits (see accompanying Gilbert and Sui abstract). These results indicate that neonatal hypothyroidism produces long-term changes in hippocampal function that can be observed using field potential analysis in vitro and in vivo; that site is critical in determining the nature of the deficit; and that neurophysiological alterations may contribute to behavioral deficits associated with developmental hypothyroidism. (Does not reflect US EPA policy).