What is it about?

Thyroid hormone is indispensable for brain development. Congenital hypothyroidism causes learning disability and motor deficits unless the proper treatment is applied as early as possible. However, the mechanism has yet to be revealed. We focused on the cerebellum, which expresses a plenty of thyroid hormone receptors and controls motor performance. Long-term depression in Purkinje cells is important for motor coordination and motor learning. Using the transgenic mice expressing a human mutant thyroid hormone receptor specifically in Purkinje cells, we examined the effect of thyroid hormone on the cerebellar functional development. Transgenic mice spent longer on walking on the ladder than wild mice did, indicating the impairment in motor coordination. Long-term depression (LTD) - inductive stimulation caused long-term potentiation. This was resulted from the low calcium level in Purkinje cells. These changes were not observed in the adult-onset mutant mice, suggesting that thyroid hormone during the development is critical for functional maturation of Purkinje cells. The present finding could be applied to other brain regions including the hippocampus which is responsible for learning and memory.

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Why is it important?

Although it is well known that thyroid horones are indispensable for brain development, we have little knowledge about how congenital hypothyroidism in neurons affects functions of the central nervous system in adulthood. The present study demonstrates a cerebellar Purkinje cell-specific developmental role of thyroid hormone in determining the direction of synaptic plasticity in adulthood. Our findings indicate that motor deficits observed clinically in congenital hypothyroidism might be a consequence of impaired LTD at parallel fiber –Purkinje cell synapses.


Our discoveries could give insight into the cellular and molecular mechanisms underlying congenital hypothyroidism–induced dysfunctions of the nervous system, including the cerebellum.

Prof. Noriyuki Koibuchi
Gunma Daigaku

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This page is a summary of: Long-term depression–inductive stimulation causes long-term potentiation in mouse Purkinje cells with a mutant thyroid hormone receptor, Proceedings of the National Academy of Sciences, November 2022, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2210645119.
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