The effects of intra-hippocampal L-thyroxine infusion on long-term potentiation and long-term depression: A possible role for the αvβ3 integrin receptor.

Although the effects of long-term experimental dysthyroidism on long-term potentiation (LTP) and long-term depression (LTD) have been documented, the relationship between LTP/LTD and acute administration of L-thyroxine (T4) has not been described. Here, we investigated the effects of intra-hippocampal administration of T4 on synaptic plasticity in the dentate gyrus of the hippocampal formation. After a 15-minute baseline recording, LTP and LTD were induced by application of high- and low-frequency stimulation protocols, respectively. Infusions of saline or T4 and tetraiodothyroacetic acid (tetrac), a T4 analog that inhibits binding of iodothyronines to the integrin αvβ3 receptor, either alone or together, were made during the stimulation protocols. The averages of the excitatory postsynaptic potential (EPSP) slopes and population spike (PS) amplitudes, between 55 to 60 minutes, were used as a measure of the LTP/LTD magnitude and were analyzed by two-way univariate ANOVA with T4 and tetrac as between-subjects factors. The input-output curves of the infusion groups were comparable to each other, as shown by the non significant interaction observed between stimulus intensity and infused drug. The magnitude of the LTP in T4-infused rats was significantly lower as compared to saline-infused rats. Both the PS amplitude and the EPSP slope were depressed more markedly with T4 infusion than with saline, tetrac, and T4 + tetrac infusion. Data of this study provide in vivo evidence that T4 can promote LTD over LTP via the integrin αvβ3 receptor, and that the effect of endogenous T4 on this receptor can be suppressed by tetrac in the hippocampus.