Functional characterization of the Caenorhabditis elegans neuropeptide F/neuropeptide Y system in olfactory long-term associative memory

Understanding how the brain processes environmental stimuli into memory is one of the fundamental challenges of neuroscience in the 21st century. Growing evidence suggests that, besides classical neurotransmitters, neuropeptides play central roles in cognitive functions. In particular, the neuropeptide F (NPF)/neuropeptide Y (NPY) system has been identified as fundamental modulator of certain types of associative memory in Drosophila and mice, although the specific regulatory mechanism is poorly explored. Since the ability to learn from prior experiences evolved early in evolution, the “mini-brain” of the small roundworm Caenorhabditis elegans has proven to be ideally suited to address this fundamental neurobiological question on a cellular level. This organism exhibits several types of complex behaviours among which the ability to associate feeding state with odorant sensation, leading to a long-term modification of chemotaxis towards that odorant. Among all de novo synthesised proteins that play a crucial role in establishing long-term memory, the cAMP response element-binding protein (CREB) is one of the best known. I have recently demonstrated that the activation of CREB specifically occurs after olfactory long-term associative memory (LTAM) formation in wild-type worms. Next in my project, I will use a pCRE::GFP reporter to in vivo monitor CREB activation pattern during an olfactory assay in wild-type and NPF/NPY mutants, adding valuable information about the LTAM formation process to the canonical behavioural assay evaluation. The NPF/NPY system comprises three orthologous C. elegans receptors and their ligands have recently been characterized in our lab. Comparison between normal and mutant neuronal activation patterns, together with neuropeptide and their G-protein coupled receptors (GPCRs) localization analysis, will provide information about the neurons in which NPF/NPY neuropeptidergic control is fundamental for olfactory LTAM formation.status: publishe