Dickkopf-1 and Norrin Suppress Long-Term Potentiation in Vivo in the Rat Hippocampus

Abstract

The Wnt signal pathway plays a significant role in regulating synaptic plasticity. We have previously shown that chronic suppression of the Wnt cascade induces impairment of long-term potentiation (LTP) in vivo, while chronic overexpression of Wnt3 protein is accompanied by a transient increase in LTP amplitude. The aim of the present work was to study the effects of different doses of the Wnt signal pathway inhibitor Dickkopf-1 (Dkk1) and the Wnt signal pathway activator Norrin on LTP in vivo. Intracerebroventricular injection of both Dkk1 and Norrin induced suppression of LTP in vivo. As in the case of chronic suppression of the Wnt cascade, both effects were accompanied by decreases in the paired facilitation coefficient to the level of tetanization, evidencing the involvement of the presynaptic apparatus in the induction of LTP. These results provide grounds for suggesting that the effects of different Wnt signal pathway modulators on synaptic plasticity are based on common presynaptic rearrangements.