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 D 1 and D 5 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 μ m 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.