Thyroid hormone (TH) is essential for normal brain development. Disruption of TH action during perinatal period causes abnormal brain development. However, the precise role of TH in the developing brain has not yet been fully understood. TH action is mainly exerted by binding to the nuclear TH receptor (TR), which is the ligand-regulated transcription factor. To clarify the mechanism of TH action in brain, we have generated a transgenic mouse expressing a human dominant-negative TR1 (Mf-1) specifically in the cerebellar Purkinje cell (PC) (Yu et al. 2015), which is the only output neuron in the cerebellum to control motor performance. Using this animal model, we further clarified the mechanism. Although cerebellar morphogenesis as well as various gene expressions retarded during perinatal period, these were returned to be normal at pubertal age. Neverthless, motor performance tests revealed the impairment in motor coordination and motor learning in Mf-1 mice. The electrophysiological study at synapses between parallel fiber (PF) and PC showed that long-term synaptic plasticity expressed as long-term depression (LTD) was postsynaptically impaired in the PC of Mf-1 mice, whereas presynaptic short-term plasticity expressed as paired pulse facilitation was intact. Single-cell RT-qPCR revealed the decrease in the mRNA level of sarcoplasmic reticulum Ca2+-ATPase 2 (SERCA2), a calcium transporter located in the endoplasmic reticulum, indicating the disruption of Ca2+ mobilization in PC to produce LTD. Thus, the motor impairment in Mf-1 mice could be attributed to PCs with TR mutation through the disrupted cellular basis. The present study may suggest that the impairment of long-term plasticity in PCs would be one of the contributing factors to motor impairment in resistance to thyroid hormone (RTH) patient.