Community Research and Development Information Service - CORDIS



Project ID: 340318
Funded under: FP7-IDEAS-ERC
Country: Belgium

Mid-Term 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 aim to acquire a detailed understanding of how different sensory cues are processed and integrated by neuropeptides and their neurons during learning and memory formation. We do 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 higher organisms. Therefore, findings from C. elegans neuroscience may have profound implications for understanding our own brain functions.
In this first half of the project we successfully cloned 26 G protein-coupled receptors (GPCRs) with homology to receptors that are involved in the control of learning and memory in humans or other research models. Currently, we successfully identified a peptide ligand for 12 of these 26 GPCRs in our in cellulo reverse pharmacology assay. In addition, we have also deorphanized over 15 other C. elegans neuropeptide GPCRs.
From this set we discovered that mutants of distinct neuropeptidergic systems displayed significantly altered learning behaviour when compared to wild type worms in our salt-food association assays. For this, and further in depth analysis, we have developed and implemented automated video tracking software that allows to continuously track the displacement and associative behavioural response of individual worms over time in detail.
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. This is a first important step in uncovering the neuronal circuits underlying the associative behavioural responses.
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 now allows us to confirm the specific involvement of the previously identified cells in learning or ‘memory’ retrieval. At this time we successfully targeted neurons for optogenetic silencing and confirmed their involvement in experience-dependent NaCl chemotaxis and gustatory plasticity.
Finally, we discovered that the long-term memory generated of salt-food associations does not involve a well-described transcription factor involved in long-term memory. Since activation of transcription and translation is required for memory formation in this assay, this surprising find may lead us to the novel molecular factors in the consolidation of long-term memory.

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