Dual and opposing modulatory effects of serotonin on crayfish lateral giant escape command neurons

Serotonin modulates afferent synaptic transmission to the lateral giant neu rons of crayfish, which are command neurons for escape behavior. Low concen trations, or high concentrations reached gradually, are facilitatory, where as high concentrations reached rapidly are inhibitory. The modulatory effec ts rapidly reverse after brief periods of application, whereas longer perio ds of application are followed by facilitation that persists for hours. The se effects of serotonin can be reproduced by models that involve multiple i nteracting intracellular signaling systems that are each stimulated by sero tonin. The dependence of the neuromodulatory effect on dose, rate, and dura tion of modulator application may be relevant to understanding the effects of natural neuromodulation on behavior and cognition and to the design of d rug therapies.