DESCRIPTION (provided by applicant): Neural networks that drive rhythmic motor patterns (such as chewing, breathing, swimming, locomotion, and heartbeat in some) need to produce stable activity throughout the lifetime of the animal. Neuromodulators that modify these rhythms should also have reliable, predictable responses. The network that drives rhythmic chewing and food filtering in the crab stomach, the stomatogastric network, shows stereotyped activity across animals, and neuromodulators produce somewhat predictable responses in network activity. However, recent studies have demonstrated that identified component neurons in these and other networks vary considerably across animals. Theoretical work has demonstrated that similar cellular and network activity can be produced by very different conductance sets. The question arises, how does a neuromodulator produce a predictable response when its target conductances are variable from animal to animal? This will be addressed by investigating variability at the level of modulator receptors, modulatory action on target conductances, and modulatory effects on isolated neuron and network activity. In humans, it is thought that depression, schizophrenia and other mental illnesses can result from imbalances in neuromodulation, the action of chemicals that affect activity of neurons. This work investigates the mechanisms of stable neuromodulation, helping us understand how instabilities in neuromodulation might occur. We focus our studies on serotonin, whose imbalance in humans is implicated in many mental illnesses.