Rhythmic motor acts such as breathing, chewing and locomotion are attractive for the study of how motor systems are organized and modulated to produce adaptive output. These motor acts are generated fully or in part by rhythmically active neural networks, pattern generators, that are easily activated in the isolated CNS and are thus amenable to experimental analysis. Particularly in invertebrates, where the restricted number, large size, and identifiability of neurons offer technical advantages, progress in understanding pattern generating networks and their adaptive modulation has been rapid. We have analyzed in detail the neural network and muscular system that generates heartbeat in the medicinal leech. Reciprocally inhibitory pairs of heart interneurons pace the heartbeat rhythm. Critical switch interneurons coordinate the pattern of heart motor neurons innervating the two hearts to produce two alternating coordination states. The period and pattern of the rhythm generating interneurons and the properties of heart muscle are modulated by FMRFamide and we have identified endogenous RFamide peptides in the CNS. We have explored the ionic currents and graded synaptic transmission that contribute to rhythmicity in heart interneurons and have begun to organize these data in a realistic computer model. Here we propose to continue our study of the intrinsic membrane and synaptic properties of heart interneurons that contribute to rhythmicity, and how these properties are modulated by RFamide peptides. To guide these studies, data will be incorporated into a ongoing computer simulation. We will explore the diversity of RFamide peptides present in the CNS and their modulatory effects upon neural and muscular targets. We will analyze the membrane properties of heart motor neurons to determine how these properties transform the output of the pattern generating network of interneurons, and we will explore in detail how the alternating coordination states of motor outflow are generated and controlled. We will pursue a multifaceted approach toward these aims, involving biochemical, anatomical, and physiological techniques. By studying the mechanisms for oscillation in neural networks and for the modulation and reconfiguration of these networks in the leech, we will uncover important information applicable to other more complex motor systems.
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