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Title: Studies on the Molecular and Cellular Mechanisms underlying the process of learning and memory formation
Keywords: Learning and memory, hippocampus, mossy fibers remodelling,water maze, Cdk5, fear conditioning
Issue Date: 14-Nov-2011
Citation: ZHANG BINBIN (2011-11-14). Studies on the Molecular and Cellular Mechanisms underlying the process of learning and memory formation. ScholarBank@NUS Repository.
Abstract: There are two parts of work which have been done in this thesis to investigate the underlying mechanisms of learning process and long-term memory formation. In part I, two projects have been focused on the hippocampal mossy fibers (MFs), aiming at elucidating the role of presynaptic structural plasticity in long-term memory. In the first study, the MRI technique, in which manganese-enhanced magnetic resonance imaging (MEMRI) is employed, has been implemented to detect the learning-induced MFs remodeling during the spatial memory formation in vivo. Using a quantitative analysis of a series of sections in the rostral dorsal hippocampus, MEMRI showed an increase in the high contrast area CA3a? area in trained Wistar rats. Besides, the hypothesis that remodeling pattern of the MFs is strain-dependent has been confirmed by comparison between two strains of rats: Wistar and Lister-Hooded (LH) rats. In contrast to Wistar, no obvious remodeling of MFs was found in trained LH. So far as we know, this is the first study to employ MEMRI to visualize the structural redistribution of the hippocampal MFs that is induced by spatial learning. In the second study, the laminar-specific Zn levels in the synapses from MFs to CA3 region of the hippocampus have been mapped and quantified in ?g/g dry weight level as well as molar concentration in wet weight level, using an alternative approach nuclear microscopy. This is the first reported data showing the Zn concentration in the three different strata (stratum lucidum SL, stratum pyramidale SO, and stratum oriens SP) of hippocampal CA3 region (Zhang et al., 2011). As the axon fibers projecting to CA3 pyramidal neurons, the MFs play a critical role in the hippocampal-related learning and long-term memory procedures. Investigations on the learning-induced presynaptic plasticity might shed lights on the complicated mechanisms underlying the hippocampal-recruited long-term memory. In part II, a mutant mouse model, heterozygous knockout mouse (Cdk5+/-) has been employed to evaluate the critical role of cyclin-dependent kinase 5 (Cdk5) in fear learning and memory. The data here has shown that deficiencies in both short-term (3 hours) and long-term (24 hours) contextual fear memory were observed as the result of reduced Cdk5 protein in Cdk5+/- mice. In addition, Cdk5+/- facilitates the extinction of contextual fear conditioning. This is the first study to use heterozygous Cdk5 knockout mice to test the hypothesis that reducing levels of Cdk5 would impair performance in contextual fear conditioning. This data is complementary to previous pharmacological studies. The mutant model Cdk5+/- employed in the study makes possible for further investigations on the different molecular mechanisms involved in amygdala-related cued- or tone-dependent fear conditioning.
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