Serotonergic enhancement of a 4-AP-sensitive current mediates the synaptic depression phase of spike timing-dependent neuromodulation.
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.
Department of Biology, Georgia State University, Atlanta, Georgia 30302-4010, USA. akira@gsu.edu
Akira
A
Sakurai
Naïm R
NR
Darghouth
Robert J
RJ
Butera
Paul S
PS
Katz
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D049871:Tritonia Sea Slug / Q000502:physiology*
D026902:Potassium Channel Blockers; D012701:Serotonin; D015761:4-Aminopyridine