Dopaminergic DA1 signaling couples growth-associated protein-43 and long-term potentiation in guinea pig hippocampus

The basic goal of the project was to determine whether dopaminergic DA1 receptor (DA1R) signaling couples growth-associated protein 43 (GAP-43; a putative “plasticity” protein) and long-term potentiation (LTP; an enduring form of synaptic plasticity). Thus, guinea pigs were prepped to stimulate the CA3 and evoke population spikes in the CA1 neurons in the hippocampus in vivo. Animals were injected with either saline or SCH23390 (a selective DA1R antagonist), 1-2 h prior to recordings. It was found that tetanic stimulation (100 Hz, 1 s, three trains at 15 s intervals) readily produced early-LTP and late-LTP in the saline group. In contrast, none of the guinea pigs pre-treated with SCH23390 developed late-LTP, though early-LTP had been present. Furthermore, both GAP-43 mRNA and protein were up-regulated after LTP induction in the saline group. However, GAP-43 protein up-regulation was blocked in animals treated with SCH23390. Anti-GAP-43 immunoreactivity was intense in CA3/CA1 synaptic regions, whereas GAP-43 mRNA hybridization was localized to somatic layers in the hippocampus. Altogether, our results suggest that dopaminergic DA1 signaling partly couples GAP-43 and LTP.