Region-specific in vivo regulation of synaptic plasticity cell signalling following learning and memory

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The long-term objectives of my research program are to elucidate the main neuronal circuits and molecular synaptic processes involved in learning and memory. Such basic research is fundamental for understanding impairments observed in brain aging and other conditions. However, it is difficult to fully establish the significance of the observed deregulations as the information on synaptic plasticity is fragmentary. Thus, our work will greatly benefit from the research proposed in the present grant. Indeed, it is essential to know which brain areas, neural systems and actual neurons do participate in these higher central nervous system (CNS) functions and in which temporal order for diverse modalities of learning and of memory mechanisms in normal conditions. The short-term goal of this application relates to the generation and exploitation of a robust transgenic rat model, which should allow the monitoring of the activation of defined neurons and brain areas in live animals, in a dynamic fashion, as a consequence of learning and memory processing. The activation of the neurons will be followed based on cAMP response element (CRE)-regulated protein synthesis, the predominant molecular pathway consolidating memory formation in the CNS. Our objectives are to 1) Generate and characterize viable transgenic (TG) models generating luminescent signals upon activation of the CRE-regulated gene expression in the brain. 2) Establish whether CRE-mediated bioluminescent and fluorescent signals in the TG rats can be monitored by advanced imaging techniques and how and where are they modulated exposing TG rats to learning and memory tasks. 3) Apply the model to investigate the extent of the participation of specific brain regions, in particular the medial prefrontal cortex, in recent memory consolidation and recall. These investigations will provide valuable novel knowledge on the complex spatial and temporal evolution of the learning and memory processes. It will constitute a considerable technological achievement and it will provide practical tools to investigate the involvement of CRE-signalling pathway in brain responses to other stimuli, thus securing Canada's position as a leader in the Neuroscience field.