D1/D5 receptor activation promotes long-term potentiation and synaptic tagging/capture in hippocampal area CA2

Hippocampal area CA2 plays an important role in social memory formation. However, CA2 is characterised by plasticity-resistant Schaffer Collateral-CA2 (SC-CA2) synapses and highly plastic entorhinal cortex-CA2 (EC-CA2) synapses. Despite abundant dopaminergic input, the relationship between dopamine signalling and area CA2 synaptic plasticity remains unexplored. Here, we show that SKF-38393-mediated dopamine D1-like receptor (dopamine D₁ and D₅ receptors (D1R and D5R)) activation differentially primes CA2 inputs in an N-methyl-D-aspartate receptor (NMDAR)- and protein synthesis-dependent manner. We defined an inverted U-shape relationship between SKF-38393 concentration and EC-CA2 potentiation. Additionally, we observed a priming effect on SC-CA2 plasticity with 50 μm SKF-38393, relieving plasticity resistance. We also demonstrated that this effect follows canonical protein kinase A (PKA) signalling. Collectively, our results show that D1R activation primes the CA2 for synaptic plasticity. Thus, we propose a link between neuropsychiatric diseases related to impaired dopamine transmission and deficits in hippocampus-dependent social memory.