Modulatory tone acts through microRNAs to exert a long-term regulatory influence on the operation of a lobster pattern generator

Georgia State University Research Foundation, Inc., Atlanta GA

Investigators

Abstract

Nerve cells in the brain are altered during physiological processes like learning and aging, or in response to new sensory experiences or perturbations. Despite these constant adjustments, neurons must also maintain key activity features that are essential for their function. The mechanisms that stabilize the identifying attributes of a given neuron are fundamentally important for nervous system performance, yet they are poorly described. Defining these cellular processes will provide insights into the organization and operation of all neural circuits, and will speak to how nervous systems can produce reliable behaviors while constantly adjusting in response to unique sets of ever-changing perturbations. This research is important because it will advance the quest to understand how the nervous system copes with variability arising from individual differences in genetic, developmental and life histories so that each individual nervous system can produce similar behaviors and respond to perturbations in a like manner. Equally important, this project is designed to train the next generation of scientists, instill a deeper appreciation of science in the public, promote minorities in science and provide a valuable scientific community resource. This project addresses how low-level modulatory tone stabilizes circuit output over the long-term using a simple model, the crustacean pyloric network. This 14-neuron circuit comprises identifiable neurons with specific activity features. A given attribute is defined by an explicit balance of conductances and is maintained by preserving its underlying conductance correlations. Low levels of monoamines can enable feedback loops that preserve conductance correlations and their corresponding activity features, even when one of the balanced conductances is persistently altered through experimental manipulation. The goal of the research is to elucidate the molecular processes involved in monoamine-enabled maintenance of conductance correlations. Recent studies show that monoamines act through microRNA to persistently influence a conductance correlation and stabilize its corresponding activity feature. A combination of molecular and electrophysiological techniques will be used to identify microRNAs that are regulated by monoaminergic tone and that maintain a specific conductance correlation. The expression of these microRNAs will then be altered to determine the effects on neuronal and circuit output. An annotated microRNA database will also be developed, hosted on a local server and made freely available.