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Mild Developmental Hypothyroidism and Trace Fear Conditioning: Role of Gender and Shock Duration.
Citation:
GILBERT, M. E. Mild Developmental Hypothyroidism and Trace Fear Conditioning: Role of Gender and Shock Duration. Presented at Society of Toxicology (SOT) Anual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
These data indicate that subtle differences in learning result from mild developmental TH insufficiency and males may be more susceptible to these insults
Description:
Rodent models of developmental thyroid hormone (TH) deficiency aptly reflect the deleterious effects of severe TH deficiencies on brain structure and function in humans. However, the impact of moderate TH insufficiencies on neurodevelopmental outcomes has proven more difficult to model. Trace fear learning was examined in adult male and female offspring following low level developmental TH disruption. Trace fear conditioning requires the involvement ofthe hippocampus by interposing a "trace" interval oftime between the conditioned (CS) and the unconditioned stimulus (US). Using a standard trace fear paradigm, additional demands were placed on the animals by 1) limiting the number ofCS (tone/light neutral stimulus) -US (footshock) pairings; and 2) addition of a noncontingent visual 'distractor' stimulus throughout training. The latter requires the engagement of the prefrontal cortex as well as the hippocampus. 0, 1 2,3, 10 ppm Propylthiouracil (PTU) was administered via drinking water to the dam from early gestation until weaning on postnatal day 21 (PN21), resulting in graded levels of T4 reduction in the dams and pups. Independent groups of adult male and female offspring were examined using one of two distract trace fear training protocols that differed in saliency of the US. Deficits in context fear learning were seen in male but not female offspring exposed to 1, 2 and 3ppm PTU relative to control (Oppm). PTU did not impact cue learning in either sex at these dose levels. At the highest dose of PTU (10 ppm), deficits were seen in both males and females in context as well as cue learning. When US saliency was increased by increasing shock duration from 0.5 to 2 sec, cue and context learning impairments were limited to high dose animals of both genders. These data indicate that subtle differences in learning result from mild developmental TH insufficiency and males may be more susceptible to these insults. (Does not reflect EPA policy).