Caenorhabditis elegans learning in a structured maze is a multisensory behavior

Abstract

Summary We show that C. elegans nematodes learn to associate food with a combination of proprioceptive cues and information on the structure of their surroundings (maze), perceived through mechanosensation. By using the custom-made Worm-Maze platform, we demonstrate that C. elegans young adults can locate food in T-shaped mazes and, following that experience, learn to reach a specific maze arm. C. elegans learning inside the maze is possible after a single training session, it resembles working memory, and it prevails over conflicting environmental cues. We provide evidence that the observed learning is a food-triggered multisensory behavior, which requires mechanosensory and proprioceptive input, and utilizes cues about the structural features of nematodes' environment and their body actions. The CREB-like transcription factor and dopamine signaling are also involved in maze performance. Lastly, we show that the observed aging-driven decline of C. elegans learning ability in the maze can be reversed by starvation.

Five Breakthroughs: A First Approximation of Brain Evolution From Early Bilaterians to Humans

“…In the context of map-based navigation, diverse and early diverging vertebrates including fish (Burt de Perera et al, 2016 ), reptiles (Wilkinson and Huber, 2012 ; Broglio et al, 2015 ), turtles (López et al, 2001 ), amphibians (Phillips et al, 1995 ), and tortoises (Wilkinson et al, 2007 ) all show the ability to build spatial maps of their environment and flexibly generate novel navigational routes to known places (Rodríguez et al, 2002 ). Model organisms for early bilaterians, such as flatworms seem to navigate only with taxis and perhaps response-based learning (Pearl, 1903 ; Luersen et al, 2014 ; Larsch et al, 2015 ; Gourgou et al, 2021 ) and show no ability to remember specific un-cued locations. Further, the neural substrates of such map-based navigation in vertebrates are uniquely vertebrate structures, such as pallial homologs of the hippocampus, suggestive of vertebrate origins.…”

3-dimensional arenas for the assessment of C. elegans behavior

“…It is reported that learning and memory decline earlier in adulthood than other physiological operations (7,37,42) and show signs of deterioration on Day 7 (37) or even Day 5 of C. elegans adult life (7). It is possible that some aspects of decision making, e.g., related to overcoming physical challenges, are affected, as well.…”

“…1A). C. elegans learning to reach a target T-maze arm is related to the 3-dimensional nature of the arena (7,8), namely walls, floor, and overall surfaces, which are perceived through multiple sensory modalities. In addition, C. elegans show a clear preference for richly patterned surfaces (9).…”

“…1). To this end, 3D-printed plastic molds are used to imprint mazes of various designs in NGM undergoing solidification (7,8). This leads to reliable, highly repeatable, and importantly, nematode-friendly assays because the generated arenas are built entirely out of NGM (Fig 1).…”

A maze platform for the assessment of Caenorhabditis elegans behavior and learning

“…Limitations include challenges in locomotion tracking and in distinguishing learning formation versus retrieval. For complete details on the use and execution of this protocol, please refer to Gourgou et al. (2021) .…”