Early postnatal hyperthyroidism alters hippocampal circuitry and improves radial-maze learning in adult mice

Abstract

Inbred mice show strain-specific differences in the hippocampal mossy fiber projection. These differences are most pronounced in the portion of the projection that forms synaptic connections with the basal dendrites of the CA3 pyramidal neurons [intra- and infrapyramidal mossy fiber (IIP-MF) projection]. We have previously demonstrated that the extent of the IIP-MF subfield is positively correlated with the capacity to perform a spatial radial-maze task and that an experimentally induced enlargement of the IIP-MFs, by means of postnatal thyroxine treatment, predicted the ability of adult two-way avoidance learning. In the present study, we tested whether this treatment would also influence radial-maze performance. Forty-five male mouse pups from the inbred strain DBA/2 (chosen because of scanty IIP-MF projection and poor radial-maze learning) were divided into three groups that received daily injections of either 2 micrograms L-thyroxine, an alkaline vehicle solution, or physiological saline. Treatment lasted from postnatal days 0 to 11. At the age of 3 months, these animals were tested in an eight-arm radial maze. The extent of their IIP-MF projections was measured by means of planimetry on Timm-stained sections. Thyroxine-treated animals made significantly fewer errors and had larger IIP-MF projections as compared to both control groups. Within each group, the individual variability of the IIP-MF projection was significantly and positively correlated with performance. We conclude that experimentally modified IIP-MF projections mediate processes underlying spatial working memory. It would appear that the hippocampal circuitry alterations induced by postnatal hyperthyroidism can counteract a hereditary lack of talent, albeit only partially and in selected populations.

Axon Pruning in the Developing Vertebrate Hippocampus

“…In addition to these inherent genetic differences in IPB length, changes in IPB length have been induced in animals with over-exposure to certain hormones or endocrine tissues. It was observed that hyperthyroidism in mice induced by daily injections of thyroxine from postnatal day 0 (P0) to P11 resulted in an increased IPB area [Schwegler et al, 1991]. Further, the hyperthyroid animals in this study had fewer errors in a radial maze task than controls, which is in agreement with the performance of mice with a long IPB mentioned above.…”

Thyroid hormones states and brain development interactions

“…Transient neonatal hyperthyroidism produces an altered hippocampal morphology with larger mossy fiber terminal fields in the hippocampal CA3 region (Lauder and Mugnaini, 1977; Lipp et al, 1988). These morphological changes are accompanied by an improvement of spatial memory in the radial maze, but there is also an impairment of two‐way active avoidance learning in the shuttle box (Lipp et al, 1988; Crusio and Schwegler, 1991; Schwegler et al, 1991). Thus, thyroid hormones influence both cognitive (spatial learning, two‐way avoidance learning), and emotional factors (two‐way avoidance learning).…”

Behavioral phenotyping of mouse models of Parkinson's disease

“…After each test session, the mice are evaluated for three parameters: working memory errors, reference memory errors, and total arm entries. Working memory errors are classified as reentries into baited arms that had been previously entered during the test session, and reference memory errors are classified as entry into non-baited arms [104, 105]. The mice were considered to have learned the task when the number of working memory errors reached zero and the number of reference memory errors is one [103, 105].…”