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K2P channels in sensory transduction and neuromodulation

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Abstract: K2P -family potassium channels are expressed throughout the nervous system, where they are thought to regulate neural excitability either as leak channels or in response to stimuli. Despite their prevalence, the roles that K2P channels play in intact neural circuits and in behavior remain poorly understood. I will discuss two studies of the genetics of C. elegans food-response behaviors that reveal functions for K2P channels in neural circuits that generate modulated behaviors. The first study found that K2P channels tune mechanosensory neurons that mediate tactile food-sensing and control locomotion. The second study identified different K2P channels as regulators of neuropeptide release from interneurons that couple food-sensing to reproductive behavior. These studies illustrate how K2P channels can exert strong and specific effects on neural circuits and provide a blueprint for identifying molecular mechanisms that control K2P channels in vivo.

Background to Research: Caenorhabditis elegans is a free-living microscopic roundworm. Its nervous system is small and only contains a few hundred cells. Despite this anatomical simplicity, the C. elegans nervous system displays genetic and neurochemical complexity that rivals that of much larger nervous systems. Importantly, stereotyped behaviors are generated by specific circuits and the neurotransmitter signaling systems they use. Genetic studies of these behaviors can identify molecules required for critical modes of neurochemical signaling, for example signaling by serotonin, dopamine, and neuropeptides. Understanding the molecular underpinnings of these signaling systems will advance the development of new psychopharmacology for the treatment of a host psychiatric and neurological diseases.

Our studies of neurochemical signaling have led us to also study the development of neural circuits that use neuropeptides to control behavior. As the nervous system develops, neurons acquire remarkable and highly specialized physiology. Many neurodevelopmental disorders are caused by defects in this process, which motivates our interest in understanding the molecular mechanisms that generate specialized neuron-types during development. As models for the study of neural development, we have selected a set of sensory neurons that detect respiratory gases and release neuropeptides to control behavior.

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