Fast updating feedback from piriform cortex to the olfactory bulb relays multimodal identity and reward contingency signals during rule-reversal

Diego E. Hernandez, Andrei Ciuparu, Pedro Garcia da Silva, Cristina M. Velasquez, Benjamin Rebouillat, Michael D. Gross, Martin B. Davis, Honggoo Chae, Raul C. Muresan () and Dinu F. Albeanu ()
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Diego E. Hernandez: Cold Spring Harbor Laboratory
Andrei Ciuparu: Transylvanian Institute of Neuroscience
Pedro Garcia da Silva: Cold Spring Harbor Laboratory
Cristina M. Velasquez: Cold Spring Harbor Laboratory
Benjamin Rebouillat: Cold Spring Harbor Laboratory
Michael D. Gross: Cold Spring Harbor Laboratory
Martin B. Davis: Cold Spring Harbor Laboratory
Honggoo Chae: Cold Spring Harbor Laboratory
Raul C. Muresan: Transylvanian Institute of Neuroscience
Dinu F. Albeanu: Cold Spring Harbor Laboratory

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract While animals readily adjust their behavior to adapt to relevant changes in the environment, the neural pathways enabling these changes remain largely unknown. Here, using multiphoton imaging, we investigate whether feedback from the piriform cortex to the olfactory bulb supports such behavioral flexibility. To this end, we engage head-fixed male mice in a multimodal rule-reversal task guided by olfactory and auditory cues. Both odor and, surprisingly, the sound cues trigger responses in the cortical bulbar feedback axons which precede the behavioral report. Responses to the same sensory cue are strongly modulated upon changes in stimulus-reward contingency (rule-reversals). The re-shaping of individual bouton responses occurs within seconds of the rule-reversal events and is correlated with changes in behavior. Optogenetic perturbation of cortical feedback within the bulb disrupts the behavioral performance. Our results indicate that the piriform-to-olfactory bulb feedback axons carry stimulus identity and reward contingency signals which are rapidly re-formatted according to changes in the behavioral context.

Date: 2025
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DOI: 10.1038/s41467-025-56023-5

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