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

Eur J Neurosci. 2010 Aug;32(4):598-605. doi: 10.1111/j.1460-9568.2010.07312.x. Epub 2010 Jul 14.


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 Ca(2+) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism
  • Cell Membrane / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dopamine Agonists / pharmacology
  • Enzyme Activation
  • Female
  • Hippocampus* / cytology
  • Hippocampus* / drug effects
  • Hippocampus* / physiology
  • Humans
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Male
  • Patch-Clamp Techniques
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D5 / metabolism*
  • Synapses / physiology*


  • Dopamine Agonists
  • Receptors, Dopamine D1
  • Receptors, Dopamine D5
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium