Learned Modulation of Innate Odor‐Driven Behavior Requires the Orbitofrontal Cortex

Abstract

Animals use a combination of innate and learned behaviors to survive. Innate behaviors do not require experience and drive stereotypical, hard‐wired responses to particular environmental cues, such as predator odor. However, learning provides a mechanism to integrate past experience and even modulate innate behaviors. We have created a behavioral paradigm to study the learned override of mouse aversion to the fox odor, TMT. The ability of the brain to suppress innate aversion in favor of a learned attraction is a form of executive control. What are the neural circuits involved in this behavior? Our previous work demonstrated that a third order olfactory brain region, the cortical amygdala, mediates innate responses to odor. We hypothesized that a higher order structure should be required to suppress innate aversion and reinforce a positive value. A likely candidate is the orbitalfrontal cortex (OFC), which receives olfactory input from piriform cortex and has outputs to the innate pathways and reward circuitry. The OFC is implicated in executive functions such as value reassignment. We have tested the role of the OFC in modulation of behavioral response to fox odor.We designed a two‐port decision making task to measure the innate response of mice to attractive or aversive odor stimuli. When odor is paired with an equal water reward at each port, water restricted mice prefer the port with the attractive rose odor, 2‐phenylethanol, to the TMT port. However decreasing the amount of water available at the rose port teaches mice to prefer the fox odor port. The attraction persists even in the absence of water. Thus, mice can learn to be attracted to predator odor that predicts reward.To test if the OFC is involved in this preference reassignment, we performed a loss of function experiment using optogenetic tools to suppress activity in the neurons of the OFC of trained animals. Bilateral expression of the light gated chloride pump, halorhodopsin, and optical stimulation in the OFC during an unrewarded test phase were sufficient to block the learned behavior and revert the animals to their innate behavioral response of avoiding aversive odor. These findings reveal that the orbitofrontal cortex is indeed required for the learned override of innate behavior. We next plan to record neural activity in the OFC as mice perform the learning task to reveal changes that occur in OFC to accommodate learning, and to map out the relevant downstream targets of OFC.Support or Funding InformationGrant #: 4R00DC014516‐03 from NIH National Institute on Deafness and Other Communication Disorders (NIDCD)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.