Mitochondrial calcium uniporter regulates odor learning and memory by controlling neuropeptide release

Abstract

SUMMARYDespite growing understanding of the various roles mitochondria play in neurons, how they contribute to higher brain functions such as learning and memory remains underexplored. Here, usingC. elegans,we found that expression level and activity of the mitochondrial calcium uniporter (MCU) pore forming unit MCU-1 impacts learning and memory for odors sensed by a specific sensory neuron, AWCON. Genetic and pharmacological manipulation showed that MCU-1 was required in the sensory neuron during conditioning. For aversive odor learning, MCU-1 mediates learning to 60-min conditioning by facilitating the selective release of NLP-1 neuropeptide through mitochondrial ROS production. MCU activation and neuropeptide release likely coincide with the AWC calcium peak following odor removal. We propose that mitochondria contribute to learning and memory by acting as a duration sensor to control select neuropeptide release in response to prolonged stimuli.