title: Activation of prefrontal cortical parvalbumin interneurons facilitates extinction of reward-seeking behavior.
abstract: Forming and breaking associations between emotionally salient environmental stimuli and rewarding or aversive outcomes is an essential component of learned adaptive behavior. Importantly, when cue-reward contingencies degrade, animals must exhibit behavioral flexibility to extinguish prior learned associations. Understanding the specific neural circuit mechanisms that operate during the formation and extinction of conditioned behaviors is critical because dysregulation of these neural processes is hypothesized to underlie many of the maladaptive and pathological behaviors observed in various neuropsychiatric disorders in humans. The medial prefrontal cortex (mPFC) participates in the behavioral adaptations seen in both appetitive and aversive-cue-mediated responding, but the precise cell types and circuit mechanisms sufficient for driving these complex behavioral states remain largely unspecified. Here, we recorded and manipulated the activity of parvalbumin-positive fast spiking interneurons (PV+ FSIs) in the prelimbic area (PrL) of the mPFC in mice. In vivo photostimulation of PV+ FSIs resulted in a net inhibition of PrL neurons, providing a circuit blueprint for behavioral manipulations. Photostimulation of mPFC PV+ cells did not alter anticipatory or consummatory licking behavior during reinforced training sessions. However, optical activation of these inhibitory interneurons to cues associated with reward significantly accelerated the extinction of behavior during non-reinforced test sessions. These data suggest that suppression of excitatory mPFC networks via increased activity of PV+ FSIs may enhance reward-related behavioral flexibility.
authors.affiliation: Departments of Psychiatry and Cell Biology and Physiology, University of North Carolina Neuroscience Center, Bowles Center for Alcohol Studies, and Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; Synaptic Transmission 1, Neuroscience Drug Discovery Denmark, Lundbeck, Copendhagen-Valby, Denmark 2500; and Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark 2200.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Sparta
authors.forename: Nanna
authors.initials: N
authors.lastname: Hovelsø
authors.forename: Alex O
authors.initials: AO
authors.lastname: Mason
authors.forename: Pranish A
authors.initials: PA
authors.lastname: Kantak
authors.forename: Randall L
authors.initials: RL
authors.lastname: Ung
authors.forename: Heather K
authors.initials: HK
authors.lastname: Decot
authors.forename: Garret D
authors.initials: GD
authors.lastname: Stuber
mesh_terms: D000818:Animals; D005108:Extinction, Psychological / Q000502:physiology*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D010320:Parvalbumins / Q000378:metabolism*; D010775:Photic Stimulation / Q000379:methods; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D012201:Reward
chemical_list: D010320:Parvalbumins