Reciprocal stimulation of decay between serotonergic facilitation and depression of synaptic transmission.
Serotonin can produce multiple, contradictory modulatory effects on strength of synaptic transmission in both vertebrate and invertebrate nerve circuits. In crayfish, serotonin (5-HT) can both facilitate and depress transmission to lateral giant escape command neurons; however, which effect is manifest during application, as well as the sign and duration of effects that may continue long after 5-HT washout, may depend on history of application as well as on concentration. We report that protein kinase A (PKA) signaling is essential to the production of facilitation but depression is mediated by non-cAMP/PKA signaling pathways. However, we unexpectedly found that PKA activity is essential for the decay of depression when serotonin is washed out. This, and evidence from the effects of a variety of serotonin application regimens, suggest that facilitatory and depressive states coexist and compete and that the decay of each is dependent on stimulation by the other. A computational model that incorporates these assumptions can account for and rationalize the varied effects of a wide range of serotonin application regimens.
Department of Psychology, UCLA, Los Angeles, CA 90095, USA.
Sun Hee Cho
SH
Lee
Karen
K
Taylor
Franklin B
FB
Krasne
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D003400:Astacoidea; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008954:Models, Biological; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012701:Serotonin; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide