Extrinsic neuromodulation is a general mechanism to stabilize neural network function during temperature changes

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How nerve cells in the brain deal with temperature changes is not well understood. The electrical activity that nerve cells produce rely on a well-balanced flow of ions across the cell membrane. It is this balance that is critically altered by temperature, leading to failures in neural activity and accordingly severe consequences for vitality. Many animals have evolved compensatory mechanisms allowing their brains to function over a wider temperature range. This research elucidates such evolutionary conserved mechanisms with a novel approach by studying the same nerve cells in several different species of crustaceans. Crustaceans are ideal systems to address these issues because of their large and identified nerve cells and they live at a variety of temperatures. Recognizing evolutionarily conserved mechanisms for temperature compensation is not only crucial for understanding how animals survive in continuously changing environments, they are ultimately also a prerequisite for the investigation and treatment of hyper- and hypothermia. This project will provide comprehensive training in identifying temperature effects on nerve cell physiology and in cutting-edge electrophysiology for all levels of students. Results will be disseminated publicly through Youtube and a variety of public outreach programs. Possessing compensatory mechanisms that maintain vital neuronal activity when temperature changes is critical for animal survival. Recent data from central pattern generators in the crustacean stomatogastric nervous system have shown that descending projection neurons that provide extrinsic neuromodulation to motor networks can counterbalance detrimental temperature effects in these networks. Compensation is achieved by counterbalancing temperature-dependent increases of ionic conductances, allowing for a quick and flexible response to temperature influences. Descending projection neurons are universal building blocks in the motor circuits of many taxa, and the goal of this project is to test the hypothesis that temperature compensation via neuromodulation is a widespread phenomenon and evolutionarily conserved. Experiments will be carried out on several closely and distantly related crustaceans with various evolutionary backgrounds and temperature tolerances. Specifically, extra- and intracellular recordings, including voltage- and dynamic clamp, from identified modulatory and pattern generating neurons in the stomatogastric ganglion will (1) determine temperature compensation in related species with similar temperature tolerance and (2) determine temperature compensation in distantly related species with different temperature tolerance. This study will show that neuromodulation is more than a means to increase flexibility in the nervous system in that it stabilizes neuronal activity in a functional context.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.