Oscillatory neural networks underlie rhythmic behaviors such as respiration, heartbeat, and swimming. Recent theoretical and experimental work on these networks in invertebrates has highlighted cellular mechanisms that may be critical to the origin of the oscillation. Experimental and neuromodulatory manipulations of these critical voltage- gated and synaptic conductances in the leech heartbeat network will determine their influence on the oscillation period and waveform. The relative influence of graded and spike-mediated synaptic inhibition on the cycle period will be studied experimentally by altering the maximal conductances of these two modes of inhibition. Also, the effect of varying the strength of the hyperpolarization-activated inward current, I-h, which is thought to pace the heartbeat cycle, will be tested experimentally. In addition, a search will be made for a neuromodulator of Ih. These experiments will be done in conjunction with computer simulations of the network. The previously described effects of FMRFamide modulation on the delayed rectifier, Ik1, and spike-mediated transmission will be modeled. By determining the critical cellular mechanisms involved in rhythm generation in the leech, this study may reveal potential cellular targets of neuromodulation in motor-pattern generating networks in general.
