ABSTRACT
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.
