Objective Since the discovery of the anti-NMDA receptor (anti-NMDAr) encephalitis (Dalmau et al., 2007) there has been a rapid expansion in both the number of patients diagnosed with this potentially fatal but treatable disease, and the identification of other autoimmune synaptic disorders (Lancaster & Dalmau 2012). Given the established central role of NMDAr in learning and memory, memory deficits are among the predominant symptoms of this disorder. Based on classical human studies, it is well established that the hippocampus is critical for long-term memory. Since the discovery of place-cells in the hippocampus of rodents (O’Keefe et al. 1971) the main focus of research on the neural basis of memory formation has become the understanding of how memory is encoded in the neural activity of these cells. We hypothesize that (i) NMDAr function is necessary for generation of new spatial representations of novel environments (Kentros et al. 1998) and (ii) for the retrieval of existing spatial representations on familiar environments. We will test this two-fold hypothesis using a recently established mouse model of human NMDAr antibody-mediated memory deficits (Mannara et al 2013). We will continuously inject anti-NMDAr antibodies obtained from patients with anti-NMDAr encephalitis while we image the simultaneous activity of hundreds of place-cells (Ziv et al 2013) as mice learn to navigate and differentiate between environments in order to find reward (Jercog et al. 2013). We will characterize the time course of the memory impairments and their neural-activity signature while animals are both recalling previously consolidated spatial memories and creating new ones. Our results will (i) help to understand the circuit mechanisms underlying some of the symptoms observed in patients with anti- NMDAr encephalitis and (ii) elucidate the exact role of NMDAr in the formation and retrieval of spatial memories in HP circuits. Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2013-IIF - Marie Curie Action: "International Incoming Fellowships" Call for proposal FP7-PEOPLE-2013-IIF See other projects for this call Funding Scheme MC-IIF - International Incoming Fellowships (IIF) Coordinator CONSORCI INSTITUT D'INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER EU contribution € 223 002,20 Address CALLE ROSSELLO 149 PUERTA BJS 08036 Barcelona Spain See on map Region Este Cataluña Barcelona Activity type Other Administrative Contact Rosa Vilavella (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
