A distinct distribution of functional presynaptic 5-HT receptor subtypes on GABAergic nerve terminals projecting to single hippocampal CA1 pyramidal neurons

Neuropharmacology. 2003 Jun;44(8):1022-30. doi: 10.1016/s0028-3908(03)00103-5.


5-HT is known to modify the excitability of GABAergic interneurons projecting to hippocampal CA1 neurons. In this study we investigate the presence and functionally characterize the 5-HT receptor subtypes found on the presynaptic nerve terminals of these GABAergic neurons. Using conventional whole-cell patch recording, we confirmed that the 5-HT(1A) agonist, 8-hydroxy-2-dipropylaminotetralin, presynaptically decreased electrically evoked GABA release while the 5-HT(3) agonist, m-chlorophenylbiguanide (mCPBG), presynaptically facilitated release. Using the 'synaptic bouton preparation', where CA1 neurons are acutely isolated with functional nerve terminals/boutons remaining adherent, we next showed that these receptor subtypes are found presynaptically. We next used the technique of focal stimulation of a single bouton in this preparation to further investigate the distribution of these 5-HT receptor subtypes. We found that all boutons contained inhibitory 5-HT(1A) receptors while a subset of boutons showed both 5-HT(1A) and excitatory 5-HT(3) receptors. No boutons were detected which contained only 5-HT(3) receptors. Our studies show that presynaptic 5-HT receptor subtypes are found presynaptically and are not uniformly distributed. This provides another potential mechanism whereby 5-HT can modulate GABA release and hence the excitability of hippocampal neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Evoked Potentials
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • Hippocampus / ultrastructure
  • In Vitro Techniques
  • Patch-Clamp Techniques
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / physiology*
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Presynaptic / metabolism
  • Receptors, Presynaptic / physiology*
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin / physiology*
  • Receptors, Serotonin, 5-HT1
  • Receptors, Serotonin, 5-HT3
  • gamma-Aminobutyric Acid / metabolism


  • Receptors, Presynaptic
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Receptors, Serotonin, 5-HT3
  • gamma-Aminobutyric Acid