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PROPYLTHIOURACIL (PTU)-INDUCED HYPOTHYROIDISM: EFFECTS ON SYNAPTIC TRANSMISSION AND LONG TERM POTENTIATION IN HIPPOCAMPAL SLICES.
Citation:
Gilbert, M. E. PROPYLTHIOURACIL (PTU)-INDUCED HYPOTHYROIDISM: EFFECTS ON SYNAPTIC TRANSMISSION AND LONG TERM POTENTIATION IN HIPPOCAMPAL SLICES. Presented at Society of Toxicology, San Francisco, CA, March 25-29, 2000.
Description:
Concern has been raised over endocrine effects of some classes of environmental chemicals. Severe hypothyroidism during critical periods of brain developmental leads to alterations in hippocampal structure, learning deficits, yet neurophysiological properties of the hippocampus have not been well characterized. The present study examined field potentials evoked in area CA1 of hippocampal slices derived from animals rendered hypothyroid from birth to weaning. Pregnant rats were administered 0 or 15 ppm propylthiouracil (PTU) in the drinking water from gestational day 18 until postnatal day (PND) 21. Hippocampal slices were prepared from adult male offspring between PND 200-340. Field potentials were evoked in CA1 pyramidal cell layer and the dendritic field in stratum radiatum by stimulation of stratum radiatum. Excitatory synaptic transmission was assessed by collecting input/output (I/O) functions at intensities ranging from 20-150?A. Paired pulse facilitation was assessed at intervals ranging from 20-1000ms at half maximal stimulus intensities. Finally, long-term potentiation (LTP) was induced by delivering a series of 15 5-pulse100-Hz train bursts at 200ms intervals. No differences were observed between groups in population spike (PS) or EPSP slope amplitude in baseline I/O recordings. By constrast, slight increases in peak dendritic amplitudes were observed in slices from PTU-treated animals relative to controls. Paired pulse facilitation of EPSP peak was reduced in PTU-exposed animals at all but the longest IPI. Surprizingly, PS LTP was increased in slices from PTU-exposed animals relative to controls. No differences in EPSP slope LTP were evident. These data indicate that developmental hypothyroidism produces persistent alterations in hippocampal synaptic plasticity in this brain region and demonstrate a pattern of effects distinct from that observed in dentate gyrus in vivo. This abstract does not necessarily reflect US EPA policy.