Neonatal hyperthyroidism disrupts hippocampal LTP and spatial learning.

Excess thyroid hormone at an early stage of development produces marked neurochemical and morphological alterations in the rat hippocampal formation. In order to better understand the functional significance of these changes, we tested adult rats treated neonatally with triiodothyronine (T3), and their control litter mates, in a spatial learning task and for the induction of long-term potentiation (LTP) in the dentate gyrus (DG) of the hippocampal formation. The T3-treated rats were significantly impaired in their performance on the spatial task in comparison to their matched controls. Similarly, the efficacy of LTP induction was significantly attenuated in the T3-treated animals. Further, a significant correlation was obtained between LTP induction and performance on the spatial learning task. Thus, a brief neonatal excess of thyroid hormone produces impairments in spatial learning along with decreases in LTP, long held as a model of learning and memory. This relationship provides a unique opportunity to study associations between behavioral, physiological, pharmacological and morphological processes intimately associated with the hippocampal formation.