SAFETY SIGNAL LEARNING IN MONKEYS: CORTICAL REGULATION AND ITS DEVELOPMENT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project is to modify our existing fear inhibition paradigm to permit its use longitudinally to investigate which specific orbital frontal sectors are involved in the acquisition and expression of conditioned inhibition in adult monkeys and second to follow longitudinally when orbital frontal regulation of conditioned inhibition emerged in primates of both sexes. We assembled the two new conditioning boxes and have modified these boxes to use multiple images as cues delivered via a computer screen instead of tone, light and fan as in our earlier studies. We have also programmed the delivery of the conditioned and unconditioned stimuli and have already acquired 9 female and 2 male monkeys. The paradigm was piloted on one monkey that learned successfully the task. Six new monkeys (2 males and 4 females) were started but only one of them was able to learn the task. We are now re-testing these animals using simpler visual stimuli (red square, yellow circle and blue star) instead of the more complex stimuli. Two have now learned the task and will progress on the test using different easy stimuli. Excessive fear and anxiety, along with an inability to overcome these emotions, are defining characteristics of many psychiatric disorders such as phobias, panic disorder, and posttraumatic stress disorder. Primate models of fear conditioning and fear inhibition provide useful tools to establish critical translational approaches to eventually develop novel treatments for disorders such as PTSD, where an inability to respond to safety signals is one of its core symptoms