Saturday, April 20, 2024
4/20/2024
Summary Learning and memory storage is a complex process that has proven challenging to tackle. Despite significant progress in understanding classical conditioning, it is likely that in nature, the instructive value of reinforcing experiences is acquired rather than innate. In other words, many of our learning experiences occur by inferring value from a previously associative structure of the environment and not by the mere contiguity of conditioned and unconditioned. This is relevant because the association between seemingly neutral stimuli expands the gamut of possibilities to create meaningful associations and generalizations and increases the predictive power of moment-by-moment experiences. High-order conditioning falls within this category of learning. This proposal aims to understand the biological basis of olfactory sensory preconditioning, a form of high-order conditioning. Specifically, we will use behavioral and functional imaging techniques combined with neuronal and genetic manipulations, including optogenetics, to define the basic rules and dynamics of sensory preconditioning. We will also test the dopamine modulation’s role in this form of learning. Finally, we will test the hypothesis that olfactory representations are altered during sensory preconditioning and that this altered representation is fundamental for forming associations between valueless stimuli. The long-term goal of this proposal is to gain knowledge on the biological basis of how our brain achieves sensory preconditioning. This proposal is highly significant because there is a big gap in our knowledge of biological basis of high-order conditioning. In addition, understanding how memories are encoded and disrupted in brain disorders is a prerequisite to the rational design of treatments for memory impairment. Our understanding of memory formation is based heavily on classical conditioning research. Nevertheless, we argue that high-order conditioning is more relevant than Pavlovian association in real naturalistic situations. The results of the present studies will provide guideposts for future research into the neurobiology of memory formation during high-order conditioning. The project will support our long-term goal of understanding memory down to the single-cell and subcellular levels, contributing to the knowledge base necessary for the rational development of novel treatments for memory impairment.
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