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Elucidating the mechanisms and dynamics of olfactory memory formation in Caenorhabditis elegans


Learning and memory are essential for survival—organisms must respond to their environment and update their knowledge accordingly. Memories undergo multiple stages before being stored long term: acquisition, consolidation, and maintenance. Various factors contribute to long-term memory formation, including sleep, synaptic plasticity, and molecular mechanisms. Sleep is thought to drive memory consolidation by promoting synaptic plasticity. However, the exact molecular, cellular, and synaptic mechanisms occurring during sleep to drive memory maintenance are not well known. To achieve single-cell and synaptic resolution of memory in a genetically-amenable organism, I utilized C. elegans and an odor spaced-training long-term memory paradigm. I show that sleep post training is required to consolidate the odor memory. I found that one specific interneuron (AIY) is required for long-term odor memory maintenance, and that synapses between that interneuron and one olfactory sensory neuron (AWC) are decreased after the long-term memory is formed, only in animals that slept. In addition, I found that the human transient receptor potential vanilloid (TRPV) channel osm-9, an ortholog of human TRPV5 and TRPV6, is required specifically for memory consolidation in order to establish this long-term olfactory memory, independent of sleep. Understanding the mechanisms underlying how learning and memory are mediated is important to understand how organisms learn from their environment to ensure survival, as well as what happens when these processes go awry, such as in the disease context. Expanded CGG repeat RNAs from the fragile X mental retardation 1 (FMR1) gene are present in the brain of patients with fragile X and fragile-X tremor/ataxia syndrome (FXTAS). We show that when human FMR1 with these expanded RNA repeats is expressed in C. elegans olfactory sensory neurons, that it blocks short-term odor memory. Behavioral plasticity perturbations are also observed in FXTAS patients, such as altered prepulse inhibition. We find that this aberrant plasticity requires the miRNA-Argonaute pathway. Thus, these studies may help to understand the molecular and cellular mechanisms and dynamics of how neural plasticity drives learning and memory, and what happens molecularly in diseases that limit plasticity.

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