Cognitive Control of Olfactory Learning

Animals adapt to ever-changing environments by rapidly modifying their behavior to accommodate the evolving rules and contingencies of their current situations. In simple learning, the same stimulus always precedes the same reinforcement, likely engaging plasticity in connections between brain regions representing the stimulus and downstream areas that drive the response. However, animals regularly face stimuli in multiple situations in which the relationships between these stimuli and reinforcement rapidly change. For example, the smell of smoke outside represents a campfire and its warmth, but the smell of smoke in one’s home represents a fire from which to flee. Thus cognitive control is often required to weigh context when deciding how to react in response to the same sensory stimulus.

A growing body of evidence implicates the prefrontal cortex (PFC) in mediating context-dependant or rule-guided adaptive behaviors. Our observation that activation of ensembles of neurons in the piriform cortex is sufficient to generate context-dependent learned behaviors in the absence of any external sensory input, suggests that all the components that are necessary to produce these behavioral responses are contained within the piriform and its downstream output regions. Our tracing studies revealed that one of these output regions is the PFC. This raises the possibility that olfactory sensory representations in the piriform are relayed to the PFC to be bound with context- or task-related information, a necessary step in guiding adaptive behaviors. This direct connection from the primary sensory cortex to the PFC, a feature absent in other sensory systems, makes the olfactory system uniquely amenable to characterizing how sensory information maps to the PFC. Furthermore, our ability to entrain an ensemble of piriform neurons to drive learned behaviors in the genetically malleable mouse model allows us to manipulate PFC circuitry with unprecedented precision. Thus, we are asking whether the piriform-to-PFC connections are involved in adapting and modifying behavioral responses to environmental context. We hope that his work will contribute to our understanding of how the PFC develops the representations required to produce contextually appropriate responses and ultimately how these representations might be used to modulate learned behaviors.