Cortical-bulbar feedback supports behavioral flexibility during rule reversal

Animals flexibly adjust their behavior to adapt to environmental changes. Mice excel at recognizing odorants in complex sensory conditions; however, little we know about: (1)how sudden changes in stimulus contingency modify odorant representations and (2)how changes in odorant representations causally relate to behavioral adjustments. The olfactory bulb(OB) relays odor-triggered information to higher olfactory areas, including the piriform cortex(PCx). The PCx receives input from association areas(e.g., orbitofrontal cortex) and sends dense feedback that selectively modulates one of the OB output channels(mitral cells). Therefore, PCx is in an ideal position to integrate sensorial input and behavioral contingencies and modulate the OB output in tune with the animal behavioral goals.
To study the role of cortical-bulbar feedback in supporting flexible behaviors, we trained mice in a Go/No-Go task with rule reversal guided by odorant and sound-tone cues. Within the same session, reward contingencies were reversed across blocks of contiguous trials, rewarding either the odorant or tone cues depending on the block rule and animal decision(report lick). Using multiphoton microscopy, we monitored cortical-bulbar feedback bouton responses(GCaMP5/7b) of anterior PCx(aPCx) neurons from mice engaged in the task.
Cortical-bulbar feedback boutons exhibited dense and diverse responses aligned with different trial epochs. Cortical-bulbar feedback activity changes mirror the task block structure and display a high correlation for the same behavioral contingency. The response changes observed after each rule reversal slightly lagged in updating accordingly to the behavioral switch. Multilayer perceptrons trained to decode stimulus identity and behavioral contingency rapidly increased their performance during cue delivery and before the animal’s decision. Optogenetic suppression experiments(Jaws) of cortical-bulbar feedback suggest that mice rely on cortical feedback to adapt their behavior after each rule switch.
Our results indicate that cortical-bulbar feedback multiplexes information about stimulus identity and behavioral contingency and is rapidly re-formatted according to changes in contingency rules.