Aim: Imbalances in plasma thyroid hormone levels cause changes in synaptic response, resulting in impairments in learning and memory. It is not well understood how the excess of these hormones (T3 and T4 hormones), which modulate gene transcription, affects gene expression after high-frequency stimulation (HFS). Therefore, in this study, it was aimed to investigate the transcriptional changes accompanying long-term potentiation (LTP) in genes related to neurodegeneration in rats with hyperthyroidism. Materials and Methods: 12 male Wistar-albino rats were used in the study. The rats were divided into two groups as control and hyperthyroidism groups. To induce hyperthyroidism, L-tyroxine was administered intraperitoneally at a dose of 400 µg/kg/day for 21 days, starting on the 39th day. To investigate LTP, when rats were 60-day-old, LTP was induced by giving HFS at 100 Hz for 1 second at 5-minute intervals after 15 minutes of basal recording to the perforating pathway and the excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude were recorded in the granule cell layer of the dentate gyrus. The mRNA levels of genes related to neurodegeneration in stimulated hippocampus were measured by reverse transcription-polymerase chain reaction method. Results: After HFS, LTP was induced in the control group at the EPSP slope, while LTP was not induced in the hyperthyroid group. However, LTP was induced at the PS amplitude in both groups. In hyperthyroid rats, Gsk3β, P35(Anxa) Calpn1 and Bace1, Psen2-mRNA levels were not significantly different compared to the control group, while Akt1, Cdk5 and Mapt-mRNA levels were found to be increased significantly compared to the control group (p<0.05). Conclusion: These findings suggest that the excess of thyroid hormone during neuronal plasticity partially alters the expression of genes related to neurodegeneration.