Multiple memory networks: plasticity mechanisms, representations, and behaviour

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Empirical and theoretical work suggests that the organization of memory in the mammalian brain and the neural systems that mediate them play a pivotal role in our thoughts, emotions, choices, actions, and our personalities. The theory guiding this research program is that memory function in the mammalian brain is organized into groups of neural networks mediating different memory functions. Within this organization, normal thought and behaviour arise from cooperative and competitive interactions between these different systems.      For this proposal we focus on the functions of a memory network centered on the hippocampus (HPC) and associated plasticity mechanisms. This work emerged from controversies over the role of N- methyl-D-aspartic acid (NMDAR) mediated long-term potentiation (LTP) in the acquisition of spatial information during training on the Morris water task (MWT). Seminal behavioural pharmacology work showed that NMDAR LTP was necessary for acquisition of the MWT but not expression. However, later research revealed that spatial learning in the MWT is rendered NMDAR independent when pre-training is employed.      We developed a behavioural paradigm in an attempt to understand why NMDAR-mediated plasticity mechanisms are involved in some variants of place learning and not others. The pattern of effects led us to several hypotheses about the role of HPC NMDAR in spatial learning. HYPOTHESIS: HPC representations formed during rapid new learning using familiar or new spatial information will differ in content and underlying neurobiological mechanism. New learning with familiar information will induce rate remapping processes that are not NMDAR dependent, while new learning with new information will induce global remapping. Rate remapping can be supported by non-NMDA forms of LTP mediated by voltage-gated calcium channels (VGCC) while global remapping requires both forms of plasticity. We will use electrophysiology, imaging, behavioural pharmacology, and immunohistochemistry techniques to assess how HPC representations will differ when learning uses familiar vs. new spatial information.      IMPACT: There has been significant efforts aiming to account for how behaviour is shaped by exposure to specific events, the neural networks responsible, and the biochemical mechanisms supporting these functions. Understanding how the HPC represents different experiences used by individuals to navigate a complex world and the underlying neurobiological mechanisms supporting these functions is fundamental to understand the underpinnings of normal and abnormal manifestations of behaviour. This work will further our understanding of the nature and causes of psychiatric disorders including addiction, anxiety, post-traumatic stress disorder, and obesity. We seek to provide key information about when HPC NMDAR-mediated LTP is required for learning in the mammal as there is still significant room for discovery, innovation, and impact in this area.