Deconstructing neural circuits underlying olfactory episodic memory

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Concept: Where and when did I smell that apple pie before? Ability to detect chemical signals in the environment and remember elements of a unique olfactory event is essential for making sense of the present, forming predictions about the future, and the selection of behaviours for survival and reproduction. For example, animals use olfaction and olfactory memory to locate predators, foods, social hierarchy, mating partners, and caregivers. Decades of research have revealed how specific odours are detected and processed by the olfactory system to perceive odours. However, it remains unknown how our brain forms a memory of detailed contextual information about unique olfactory events. To address this knowledge gap, we have pioneered a model system for olfactory episodic memory, constituted by a hard-wired connectivity between the hippocampus and the olfactory cortex, and a robust behavioural readout of contextual elements of olfactory memory. In the present proposal, we use this system to study a neural mechanism underlying olfactory episodic memory. Objectives: To understand how olfactory memory is formed and expressed in brain at circuit level, we use a combination of anatomical tracing, activity-dependent cell labeling, and live brain imaging and manipulation. By combining the preliminary findings of the above approaches, we have recently discovered that neural signals from hippocampus are spatially organized within the olfactory cortex to carry distinct spatial and temporal context of olfactory memory. As a five year NSERC proposal, we will focus on understanding how olfactory events are represented by specific cells within the olfactory cortex and demonstrate that their activity can be manipulated to alter the memory. Next, we will expand our findings to investigate how the activity of olfactory cortex evolves over time to faithfully recapitulate olfactory memory. Our specific short-term objectives are: Study 1. We will identify the olfactory memory trace that is represented by the anterior olfactory nucleus (AON) using the TRAP approach. Study 2. We will determine a causal contribution of the AON in olfactory memory using optogenetic manipulation. Study 3. We will demonstrate how a unique olfactory memory trace is formed and stabilized within the AON, and later reactivated during memory recall in a hippocampus-dependent manner using calcium imaging. Significance: Numerous human brain imaging studies have shown that olfactory areas are reactivated during recollection of olfactory episodes. However, the underlying neural mechanism remains unknown. The proposed research program will demonstrate for the first time that the AON is the storehouse of olfactory episodic memory, and provide a novel insight into the universal mechanism of episodic odour memory formation and recall. Given its novelty and the expected conceptual advance, we expect the proposed research to be of great interest to many fields in the natural sciences and engineering.