Serotonergic enhancement of a 4-AP-sensitive current mediates the synaptic depression phase of spike timing-dependent neuromodulation

J Neurosci. 2006 Feb 15;26(7):2010-21. doi: 10.1523/JNEUROSCI.2599-05.2006.


The mechanism underlying spike timing-dependent neuromodulation (STDN) was investigated in the opisthobranch mollusc Tritonia diomedea. The serotonergic dorsal swim interneurons (DSIs) dynamically modulated the synaptic output of ventral swim interneuron B (VSI); immediately after DSI stimulation, there was a potentiation of VSI synaptic strength followed by a longer-lasting synaptic depression. The potentiation phase of STDN was unaffected by spike broadening produced by the potassium channel blocker 4-aminopyridine (4-AP). In contrast, the depression phase was eliminated by 4-AP. Bath-applied serotonin (5-HT) decreased VSI spike duration and increased the magnitude of the A-current (IA), a voltage-dependent, transient, outward current. 4-AP preferentially blocked IA and prevented the spike narrowing caused by 5-HT, uncovering the full extent of 5-HT-induced synaptic potentiation. A consistent correlation was observed between IA and spike duration, but the correlation between synaptic strength and spike duration differed between preparations. Conductance-based simulations showed that the magnitude of A-current conductance could affect spike duration and gave an estimation of the change needed to produce spike narrowing. An artificial IA introduced into the VSI in the presence of 4-AP by means of the dynamic-clamp technique restored spike duration and gave a further approximation of the magnitude of modulation needed for spike narrowing. Together, these results suggest a mechanism for STDN: the DSIs release 5-HT, which causes a spike duration-independent enhancement of synaptic strength and a longer-lasting enhancement of IA that narrows the VSI spike and hence decreases VSI synaptic strength. Thus, STDN arises from the dynamics of independent intracellular signaling events.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Animals
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Potassium Channel Blockers / pharmacology
  • Serotonin / physiology
  • Synapses / drug effects
  • Synapses / physiology
  • Tritonia Sea Slug / physiology*


  • Potassium Channel Blockers
  • Serotonin
  • 4-Aminopyridine