Two complementary approaches, one empirical and the other modeling, are being used to investigate the neural mechanisms underlying adaptive behaviors of the marine mollusc Aplysia. Empirical studies identify and characterize neurons and circuits, and modeling studies use this empirical data to develop mathematical formalisms that realistically simulate the properties of the neurons and circuits. The models are manipulated to study the contributions of component processes to neuronal and network dynamics, to determine the extent to which the current understanding of a neural circuit is sufficient to account for features of a behavior, and to identify critical parameters that warrant additional experimental examination. This proposal requests support for modeling studies that will examine two neural circuits: one underlying the tail-siphon withdrawal reflex and the other a central pattern generator (CPG) underlying aspects of feeding behavior. Models will be based on empirical data and simulated using the program SNNAP, which was developed as a research tool to provide a flexible means for constructing realistic models of neurons and circuits. The proposal has four specific aims. 1) Examine the relative contributions of individual membrane currents to the modulation of sensory neurons. Modulation of sensory neurons by 5-- is an important cellular mechanism contributing to adaptive responses of the withdrawal reflex. At least four membrane currents in sensory neurons are modulated by 5-HT. Simulations will examine how these currents and their modulation interact to regulate properties of sensory neurons, such as spike duration and excitability. 2) Examine the roles of interneurons within the withdrawal circuit. Interneurons in this circuit produce feed forward and feedback excitation and inhibition that have both fast and slow components. Simulations will examine how these interneurons regulate features of the behavior, such as its amplitude and duration, and how their modulation contributes to behavioral plasticity. 3) Examine how rhythmic neural activity is generated in a circuit that underlies consummatory feeding behaviors. Several neurons have been identified in the buccal ganglia that are believed to function as a CPG. Simulations will determine whether these neurons and their synaptic connections are sufficient to generate patterned activity, and which cellular and synaptic properties are critical to the function of this circuit. 4) Examine how modulatory transmitters can shape the activity in the CPG. By altering synaptic strengths and membrane currents, modulatory transmitters play an important role in determining the functional organization of circuits. Simulations will examine how transmitters, which have diverse modulatory actions on the neurons as synapses within the CPG can organize the activity of this circuit. Empirical studies have provided extensive data detailing the cellular components of these two neural circuits. The proposed modeling studies will provide a synthesis of these data and additional insights into the functions of the circuits and their relationship to the behaviors. Analyses of such relatively simple neural circuits can contribute substantially to an understanding of basic principles that underlie the functions of more complex nervous systems.
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