Odor Memory Traces in the Mouse Olfactory Cortex - Supplement

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Project Summary Learning and memory are fundamental brain functions, yet their underlying cellular and neural circuit mechanisms remain poorly understood. Odor memories are exceptionally robust in humans and animals, of outstanding importance for survival and reproduction, and highly susceptible to neurodegenerative disorders including Alzheimer Disease. The olfactory (piriform) cortex has long been suggested to encode odor memories, however, the cellular substrates and circuit mechanisms of olfactory learning are unknown. Our long-term goal is to understand the cellular and neural circuit mechanisms of odor perception and memory. The objective of this proposal is to provide a mechanistic cellular/molecular understanding of how odor memories are encoded and expressed. We have developed activity-based intersectional genetic approaches in mice that allow us to identify and manipulate the activity of piriform neurons that were activated during olfactory learning. Aim 1: To determine how manipulating the activity of odor memory trace cells alters behavior. We will use genetic tagging based on cFos promoter activity (“Fos-tagging”) to visualize and manipulate the activity of piriform neurons that were activated during olfactory learning. Aim 2: To determine how olfactory learning alters the odor response properties of piriform ensembles. We will perform chronic two-photon imaging of odor-evoked activity in awake, behaving mice, before, during, and after aversive and appetitive olfactory conditioning. We will test the hypothesis that olfactory learning selectively enhances the encoding of stimulus detection and discriminability in neurons constituting an olfactory memory trace. Aim 3: To determine the molecular identity and connectivity of olfactory memory trace cells. Using our previously identified set of marker genes and single cell transcriptomics we will determine the molecular identities of piriform neurons that are activated during learning, and we will trace their axonal projections. We propose a multi-tiered experimental approach to identify the cellular substrates for olfactory learning and memory, to provide mechanistic insight into how neural circuit functions are shaped by experience. Achieving our goals requires the generation and analysis of large, multimodal data sets, including chronic in vivo calcium imaging and behavioral monitoring. We will develop robust software tools for data integration, analysis, storage, and sharing. In collaboration with experts in software engineering and computational neuroscience we have built open-source standardized code and file formats for data processing. We will enhance code robustness and integration, and we will establish cloud compatibility. We will adapt our pipeline for usage with a range of open-source software tools and provide a graphical user interface. The innovative software solutions we propose will enhance reproducibility and shareability of integrated neural activity and behavioral data, with significance to a large neuroscience user group.