2014 - Doctoral School n° 549 Health, Biological Sciences, & Life Chemistry Thesis Proposal 1. Thesis Supervisor(s): Name(s): Calandreau Ludovic and Lévy Frédéric Research Unit: UMR INRA/CNRS/University F. Rabelais-Tours/IFCE Physiology of Reproduction and Behavior Mail: [email protected] [email protected] 2. Thesis Title : Effects of chronic stress on memory and hippocampal plasticity as a function of individual emotional reactivity trait in bird 3. Summary : In adult mammals and birds the hippocampus produces and incorporates new neurons. This hippocampal neurogenesis is important for the requirement of the hippocampus to memory. Recent studies, mainly in rodents, show that chronic stress is a potent modulator of hippocampal neurogenesis. Nevertheless, characterization of the relationships between chronic stress, hippocampal neurogenesis and memory still deserve consideration in birds. The main objective of the project will be to study these relationships. Moreover, recent studies suggest that individual level of emotional reactivity may explain inter-individual differences in the adverse effects of chronic stress. Subjects with a high emotional reactivity level may exhibit the most important negative effects of chronic stress. The second objective of the project will be thus to study the relationships, in birds, between individual level of emotional reactivity and negative neurobiological and behavioral consequences of chronic stress. Task 1: Effects of chronic stress on memory depending on the individual emotional reactivity trait. The first objective of the project will be dedicated to show that emotional reactivity trait influences the detrimental effect of chronic stress on hippocampus-dependent memory. To this aim, we will use two lines of Japanese quail that have been divergently selected for their emotional reactivity level. The two lines of birds (Japanese quail with a high or low emotional reactivity trait) will be repeatedly exposed to unpredictable aversive stimuli. This procedure has been already validated and shown to be associated with the development of symptoms of chronic stress in Japanese quail (Calandreau et al., 2011; Laurence et al., 2012). The impact of chronic stress on hippocampus-dependent memory will be examined in spatial learning and memory tests. These tests will be adapted from a learning procedure we already developed for the quail and which is known to be sensitive to stress (Calandreau et al., 2011). To assess the selectivity of the effects of chronic stress, birds will be also tested in hippocampus-independent memory tests. Task 2: Effects of chronic stress on hippocampal neurogenesis depending on the emotional reactivity trait. Effects of chronic stress on cell proliferation (PCNA staining) and cell survival (BrdU staining) within the hippocampus will be studied in birds from the two selected lines by immunocytochemistry. Phenotypes of new cells will be assessed by double BrdU/DCX (immature neurons) and BrdU/NeuN (mature neurons) labelling. Task 3: Identify the causal link between hippocampal neurogenesis and hippocampal memory function in individuals with a low and high emotional reactivity trait. Hippocampal neurogenesis will be permanently blocked by continuous infusion of the antimitotic AraC into the hippocampus of birds with high and low emotional reactivity trait. The impact of decreased hippocampal neurogenesis on spatial learning and anxiety will be tested.
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