Rhythmically active neuronal networks called central pattern generators generate rhythmic motor acts, such as breathing, chewing and locomotion. The study of these networks contributes not only to our knowledge about how the nervous system programs adaptive movements but also to our understanding of the dynamics of neuronal ensembles in general. We have analyzed the network that generates heartbeat in the leech. Two segmentally repeated pairs of reciprocally inhibitory heart interneurons form oscillators that pace the rhythm. These oscillators are coupled by coordinating interneurons to form an 8-cell beat timing network. Other premotor interneurons, along with the oscillator interneurons, inhibit heart motor neurons, sculpting their activity into rhythmic bursts. Switch interneurons interface between oscillator interneurons and premotor interneurons to produce two alternating coordination modes of the motor neurons - peristaltic and synchronous. Endogenous small molecules and peptides modulate the activity (burst period and spike frequency) of oscillator intemeurons. We have used models that incorporate detailed biophysical data about intrinsic currents and synapses as tools for understanding system dynamics, to generate experimentally testable hypotheses, and to extract principles of organizations that be can be transferred to other networks. During the last grant period we produced a series of models that have led to a detailed model of the 8-cell timing network. Here we propose a series of interwoven physiological and modeling experiments aimed at understanding how leech heartbeat and rhythmic motor acts in general are generated, coordinated intersegmentally, and modulated at the network, and cellular levels. Our ultimate goal is a complete model of the heartbeat central pattern generator and its interaction with segmental heart motor neurons to produce the heartbeat motor pattern.
Our specific aims are a step-by-step process for achieving this goal: 1. To explore the intrinsic membrane and synaptic properties of oscillator heart interneurons and their modulation and to explore the importance of the morphological complexity of these neurons. 2. To determine the intrinsic properties of the heart motor neurons and the strength and dynamics of their inhibitory connections from heart interneurons and to construct a detailed model of heart motor neuron coordination by heart interneurons. 3. To accurately determine the activity phases of the entire heart interneuron ensemble and construct a detailed model of the entire heartbeat central pattern generator. This process will provide insights generally applicable to the normal functioning of motor pattern generating networks and their coordination of motor neurons that will be useful in understanding the reaction of these networks to injury and disease. ? ?
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