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The Role of Neuropeptides in Learning and Memory

Final Report Summary - PEPTIDELEARNING (The Role of Neuropeptides in Learning and Memory.)

Mounting evidence implicates neuropeptides in the regulation of learning and memory, but the molecular mechanisms underlying neuropeptide-mediated learning behaviours largely remain elusive. In this project we aimed at acquiring a detailed understanding of how different sensory cues are processed and integrated by neuropeptides and their neurons during learning and memory formation.
We have done this by studying, at the molecular level, the ‘mini brain’ of the small roundworm Caenorhabditis elegans that counts only 302 neurons. Despite its apparent simplicity, C. elegans shows different kinds of learning behaviours similar to those observed in other animals, including humans. Therefore, findings from C. elegans neuroscience may have profound implications for understanding our own brain functions.
We successfully deorphanised 66 G protein-coupled receptors (GPCRs), the majority of which display homology to receptors in humans or other research models. We discovered that C. elegans mutants of distinct neuropeptidergic systems displayed significantly altered learning behaviour when compared to wild type worms in various learning and memory assays. We developed and implemented automated video tracking software that allows to continuously track the displacement and associative behavioural response of individual worms over time. In addition, by tagging neuropeptides and GPCRs with green fluorescent protein (GFP) we mapped the (neuronal) expression sites of the components of the signalling systems of interest in C. elegans. To decode the involved neuronal circuits we implemented optogenetic technology to target single neurons for timed and temporal (de-) activation by illuminating them at a specific wavelength. This technique demonstrated the involvement of specific neuronal cells in learning and memory retrieval. In sum, the molecular mechanisms and neuronal circuits of a number of neuropeptide receptor signalling systems involved in learning and memory were unraveled in detail, including Neuromedin U, MIP, Neuropeptide F.