Objective The project targets a field of biological research which represents one of the great challenges of our time - the elucidation of the physiological mechanisms underlying learning and memory. The chosen experimental model, long-term potentiation in slices and organotypical cultures of the rat hippocampus, allows the application of a broad spectrum of advanced pharmacological and neurophysiological methods. Since LTP-like processes have been implicated in learning, factors found to affect LTP can be anticipated to modulate learning as well. Following this line, the project aims to elucidate the involvement of selected neuropeptides in the regulation of long-term potentiation in the hippocampus. It concentrates on the involvement of three neuropeptides in the regulation of the hippocampal LTP: arginine-vasopressin (AVP) and metabolites of AVP), thyrotropinreleasing hormone (TRH) and galanin.The first two peptides share the property of having pGlu on their N-terminus and resemble in this respect pGlu-dipeptides, which have been intensively investigated by the Russian project partner. Galanin, a 29 amino acid containing peptide, was demonstrated to cause an impairment of learning and memory. Its action on hippocampal LTP will be explored with the help of new, highly specific antagonists. The following questions will be addressed: are p-Glu-containing neuropeptides (AVP fragments and TRH) and galanin involved in the induction and maintenance of LTP under normal conditions? Can they restore an artificially-induced LTP-deficiency? How do they exert their action on synaptic plasticity? What are the intracellular or membrane targets of the peptides? A diversity of advanced pharmacological and neurophysical methods will be applied, e.g. use of specific antagonists of, and specific antibodies to, neuropeptides and key molecules of second-messenger cascades; fast-application system of drugs; whole-cell patch-clamp recording; fluorescence methods; confocal microscopy.The members of the Russian group will be trained in the course of the project in London and Magdeburg in modern methods such as organotypical cultures on the hippocampus and confocal microscopy. Programme(s) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Topic(s) 45 - Pharmacology Call for proposal Data not available Funding Scheme Data not available Coordinator Federal Institute for Neurobiology EU contribution No data Address Brenneckestraße 6 39008 Magdeburg Germany See on map Total cost No data Participants (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all MRC National Institute for Medical Research United Kingdom EU contribution No data Address The Ridgeway Mill Hill NW7 1AA London See on map Total cost No data Russian Academy of Sciences Russia EU contribution No data Address 103064 Moscow See on map Total cost No data
