Temperature Compensation of Neuronal and Network Function

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DESCRIPTION (provided by applicant): Temperature is a global perturbation that alters all biological reactions and processes to a greater or lesser degree. This proposal address the fundamental question of how neuronal circuits that underly behavior can be robust against temperature changes when all of the synaptic and intrinsic properties that give rise to network dynamics are altered differently by temperature. Towards this goal, experimental and computational studies of a crustacean central pattern generating network, the pyloric rhythm of the stomatogastric ganglion (STG) are proposed. Specific Aims include: studies of the effects of temperature on individual neurons and synapses of the pyloric circuit from animals acclimated to different temperatures; voltage-clamp characterization of the effects of temperature on six voltage and time-dependent membrane currents from STG neurons from animals acclimated to different temperatures; the effects of temperature on dynamic clamp constructed reciprocal inhibitory circuits made from pairs of isolated STG neurons; development of conductance-based single neuron models; and construction of pyloric network models to explore the robustness of circuit performance to altered temperature. These data will inform our understanding of how robust circuit performance is preserved across individuals and in response to alterations in the components of a circuit over time. These experiments will contribute to our understanding of how individuals with different sets of underlying circuit components can nonetheless respond robustly to many environmental perturbations. Additionally, these experiments will provide insight into the mechanisms by which high temperature may contribute to seizure and other neurological problems. PUBLIC HEALTH RELEVANCE: In humans, elevated temperatures can result in severe neurological and physiological problems, including among many, febrile seizures. The proposed work will illuminate the mechanisms by which elevated temperature can result in disordered brain activity, and is important for understanding why different individuals in the natural population respond differently to many global environmental insults.