Inactivation of the Ventrolateral Orbitofrontal Cortex Impairs Flexible Use of Safety Signals

• Published in: Neuroscience 2018-05, Vol.379, p.350-358
• Main Authors: Sarlitto, Mary C., Foilb, Allison R., Christianson, John P.
• Format: Article
• Language: English
• Subjects: Animals; Anticipation, Psychological - drug effects; Anticipation, Psychological - physiology; Association; Auditory Perception - drug effects; Auditory Perception - physiology; Avoidance Learning - drug effects; Avoidance Learning - physiology; behavioral flexibility; cognitive map; Conditioning (Psychology) - drug effects; Conditioning (Psychology) - physiology; Discrimination (Psychology) - drug effects; Discrimination (Psychology) - physiology; Electroshock; fear; Fear - drug effects; Fear - physiology; Fear - psychology; Freezing Reaction, Cataleptic - drug effects; Freezing Reaction, Cataleptic - physiology; GABA-A Receptor Agonists - pharmacology; Inhibition (Psychology); Male; Muscimol - pharmacology; OFC; Prefrontal Cortex - drug effects; Prefrontal Cortex - physiology; rat; Rats, Sprague-Dawley; safety; Visual Perception - drug effects; Visual Perception - physiology
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2018.03.037

•The neural mechanisms that allow for differential responses to alternating danger and safety signals are unknown.•Inactivation of ventrolateral orbitofrontal cortex impaired fear inhibition during fear discrimination.•Ventrolateral orbitofrontal cortex is critical to fear inhibition by safety signals. Survival depends on adaptation to shifting environmental risks and opportunities. Regarding risks, the mechanisms which permit acquisition, recall, and flexible use of aversive associations is poorly understood. Drawing on the evidence that the orbital frontal cortex is critical to integrating outcome expectancies with flexible appetitive behavioral responses, we hypothesized that OFC would contribute to behavioral flexibility within an aversive learning domain. We introduce a fear conditioning procedure in which adult male rats were presented with shock-paired conditioned stimulus (CS+) or a safety cue (CS−). In a recall test, rats exhibit greater freezing to the CS+ than the CS−. Temporary inactivation of the ventrolateral OFC with muscimol prior to conditioning did not affect later discrimination, but inactivation after learning and prior to recall impaired discrimination between safety and danger cues. This result complements prior research in the appetitive domain and suggests that the OFC plays a general role in behavioral flexibility regardless of the valence of the CS.