title: Extinction Generates Outcome-Specific Conditioned Inhibition.
abstract: Extinction involves altering a previously established predictive relationship between a cue and its outcome by repeatedly presenting that cue alone. Although it is widely accepted that extinction generates some form of inhibitory learning [1-4], direct evidence for this claim has been lacking, and the nature of the associative changes induced by extinction have, therefore, remained a matter of debate [5-8]. In the current experiments, we used a novel behavioral approach that we recently developed and that provides a direct measure of conditioned inhibition [9] to compare the influence of extinguished and non-extinguished cues on choice between goal-directed actions. Using this approach, we provide direct evidence that extinction generates outcome-specific conditioned inhibition. Furthermore, we demonstrate that this inhibitory learning is controlled by the infralimbic cortex (IL); inactivation of the IL using M4 DREADDs abolished outcome-specific inhibition and rendered the cue excitatory. Importantly, we found that context modulated this inhibition. Outside its extinction context, the cue was excitatory and functioned as a specific predictor of its previously associated outcome, biasing choice toward actions earning the same outcome. In its extinction context, however, the cue acted as a specific inhibitor and biased choice toward actions earning different outcomes. Context modulation of these excitatory and inhibitory memories was mediated by the dorsal hippocampus (HPC), suggesting that the HPC and IL act in concert to control the influence of conditioned inhibitors on choice. These findings demonstrate for the first time that extinction turns a cue into a net inhibitor that can influence choice via counterfactual action-outcome associations.
authors.affiliation: Decision Neuroscience Laboratory, School of Psychology, University of New South Wales, Kensington, NSW 2052, Australia; Brain and Mind Centre, University of Sydney, Camperdown, NSW 2050, Australia.
authors.forename: Vincent
authors.initials: V
authors.lastname: Laurent
authors.affiliation: Decision Neuroscience Laboratory, School of Psychology, University of New South Wales, Kensington, NSW 2052, Australia; Brain and Mind Centre, University of Sydney, Camperdown, NSW 2050, Australia.
authors.forename: Billy
authors.initials: B
authors.lastname: Chieng
authors.affiliation: Decision Neuroscience Laboratory, School of Psychology, University of New South Wales, Kensington, NSW 2052, Australia; Brain and Mind Centre, University of Sydney, Camperdown, NSW 2050, Australia. Electronic address: bernard.balleine@unsw.edu.au.
authors.forename: Bernard W
authors.initials: BW
authors.lastname: Balleine
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology; D003213:Conditioning, Psychological; D005108:Extinction, Psychological / Q000502:physiology*; D007266:Inhibition, Psychological; D051381:Rats
keywords: Pavlovian-instrumental transfer; conditioned inhibition; context modulation; dorsal hippocampus; extinction; infralimbic cortex