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|Title:||THE NEURONAL DYNAMICS OF SHORT-TERM ASSOCIATIVE MEMORY IN THE BUTANONE MEMORY NETWORK OF C. ELEGANS|
|Authors:||Sylvain, Angelina Sylvain|
|Publisher:||Princeton, NJ : Princeton University|
|Abstract:||The ability to make and recall associations is essential to the daily interactions with our environment. Understanding mechanisms of memory formation and maintenance is crucial to alleviating the effects of disorders that affect these processes. With their demonstrated learning and memory capabilities, known neuronal connectome, and wealth of genetic tools, Caenorhabditis elegans serve as an ideal model for the study of memory. While previous work has established the molecular mechanisms required for memory maintenance in C. elegans, the neuronal dynamics driving behavioral change are not well understood. We used a previously-established short-term associative memory (STAM) paradigm in which worms learn to associate the neutral odorant butanone with food, to investigate the neural circuit responsible for the formation of a positive odorant association. We found that STAM requires sensory function only in the sensory neurons AWC, but the neurons ASE are required for memory maintenance. We also found that interneurons downstream from AWC are not required for STAM. In order to image neuronal activity in AWCon within individual, behaving worms, we developed a microfluidic device that restricted the worm within the field of view, yet allowed sufficient movement to assess odor memory via environmental preference. Data from this system revealed that AWCON activity was indicative of behavioral performance in trained, but not naive worms. This demonstrates, for the first time, a neuronal correlate for positive associative memory in C. elegans. Finally, we probed how the loss-of-function (lof) mutation in the C. elegans insulin receptor gene daf-2 extends positive associative memory. We found that despite their daf-2(lof) mutation, the mutant worms still required translation for memory maintenance and forgetting in STAM, similar to wild-type worms. We also found that the neuron AWCON in daf-2(lof) worms was more responsive to butanone; loss of DAF-2 protein was required in AWC neurons for daf-2(lof) memory extension, and activity of AWCON was positively correlated with memory maintenance 2 hours post-conditioning. Overall, these experiments establish a foundation to probe positive associative memory at the molecular, systems, and behavioral level, to comprehend in depth the interplay that enables the plasticity needed to survive in changing environments.|
|Alternate format:||The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: catalog.princeton.edu|
|Type of Material:||Academic dissertations (Ph.D.)|
|Appears in Collections:||Neuroscience|
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