Activation of dopamine D1/D5 receptors facilitates the induction of presynaptic long-term potentiation at hippocampal output synapses

Encoding of novel information has been proposed to rely on the time‐locked release of dopamine in the hippocampal formation during novelty detection. However, the site of novelty detection in the hippocampus remains a matter of debate. According to current models, the CA1 and the subiculum act as detectors and distributors of novel sensory information. Although most CA1 pyramidal neurons exhibit regular‐spiking behavior, the majority of subicular pyramidal neurons fire high‐frequency bursts of action potentials. The present study investigates the efficacy of dopamine D1/D5 receptor activation to facilitate the induction of activity‐dependent long‐term potentiation (LTP) in rat CA1 regular‐spiking and subicular burst‐spiking pyramidal cells. Using a weak stimulation protocol, set at a level subthreshold for the induction of LTP, we show that activation of D1/D5 receptors for 5–10 min facilitates LTP in subicular burst‐spiking neurons but not in CA1 neurons. The results demonstrate that D1/D5 receptor‐facilitated LTP is NMDA receptor‐dependent, and requires the activation of protein kinase A. In addition, the D1/D5 receptor‐facilitated LTP is shown to be presynaptically expressed and relies on presynaptic Ca2+ signaling. The phenomenon of dopamine‐induced facilitation of presynaptic NMDA receptor‐dependent LTP in subicular burst‐spiking pyramidal cells is in accordance with observations of the time‐locked release of dopamine during novelty detection in this brain region, and reveals an intriguing mechanism for the encoding of hippocampal output information.