Abstract

Behavioral inflexibility is a common symptom of neuropsychiatric disorders which can have a major detrimental impact on quality of life. While the orbitofrontal cortex (OFC) has been strongly implicated in behavioral flexibility in rodents across paradigms, our understanding of how the OFC mediates these behaviors is rapidly adapting. Here we examined neuronal activity during reversal learning by coupling in vivo electrophysiological recording with a mouse touch-screen learning paradigm to further elucidate the role of the OFC in updating reward value. Single unit and oscillatory activity was recorded during well-learned discrimination and 3 distinct phases of reversal (early, chance and well-learned). During touch-screen performance, OFC neuronal firing tracked rewarded responses following a previous rewarded choice when behavior was well learned, but shifted to primarily track repeated errors following a previous error in early reversal. Spike activity tracked rewarded choices independent of previous trial outcome during chance reversal, and returned to the initial pattern of reward response at criterion. Analysis of spike coupling to oscillatory local field potentials showed that less frequently occurring behaviors had significantly fewer neurons locked to any oscillatory frequency. Together, these data support the role of the OFC in tracking the value of individual choices to inform future responses and suggests that oscillatory signaling may be involved in propagating responses to increase or decrease the likelihood that action is taken in the future. They further support the use of touch-screen paradigms in preclinical studies to more closely model clinical approaches to measuring behavioral flexibility.

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