Project Summary A key function of the nervous system is to transform sensory information from the environment into actionable percepts. In a classic hierarchical representation framework, signals from peripheral receptor neurons with simple tuning properties are transformed in primary sensory cortex to represent sensory objects. However, recent data suggest that neural activity in primary sensory cortex strongly correlates with behavior, and that sensory representations undergo large scale changes over time. We here test the hypotheses that behavioral tuning of neurons in the olfactory (piriform) cortex supports the ability to filter out signals predicted by behavior, and that coupling odor exposure to behavior stabilizes representational drift. Olfaction is an ideal model system to study sensory-behavior interactions. Mice exhibit a rich repertoire of olfactory-driven behaviors, including behaviors critical for survival and reproduction, and piriform cortex receives direct sensory inputs from the olfactory bulb and is reciprocally interconnected with higher cognitive and motor areas. We have implemented state-of-the-art experimental approaches to chronically record piriform neural activity while synchronously monitoring behaviors. Our preliminary data suggests that sniffing, facial movements, and locomotion can strongly modulate piriform neuronal activity. Aim 1: To determine whether behavioral signals in piriform cortex subserve predictive processingWe will combine two-photon calcium imaging in head-fixed mice with detailed behavioral monitoring of sniffing, facial movements including whisking, and locomotion, and we will quantify the extent to which piriform odor responses differ across spontaneously occurring behavioral states. We will then use a closed-loop experimental design to directly test whether behavioral signals in piriform cortex serve to filter out expected sensory information. We predict that neuronal responses to behaviorally coupled odors will decrease over time, while responses to behaviorally uncoupled odors will remain unaltered. Aim 2: To determine whether representational drift in piriform cortex is explained by behavioral change. We will quantify the stability of odor representations in piriform cortex, and we will test the extent to which changes in odor tuning (representational drift) can be explained by changes in behavioral state. We predict that representations of odors that consistently occur during defined behavioral states remain stable over time, while responses to behaviorally uncoupled odors will drift. Successful completion of the proposed project will provide new insight into how animal behavior shapes olfactory processing and the generation of odor representations in the mammalian cortex. Our studies will set the stage for future projects aimed at characterizing the neural circuit mechanisms underlying complex odor-behavior representations in the olfactory cortex, and the investigation of complex olfactory-dr...