title: Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility.
abstract: Dysfunction of parvalbumin (PV)-positive GABAergic interneurons (PVIs) within the prefrontal cortex (PFC) has been implicated in schizophrenia pathology. It is however unclear, how impaired signaling of these neurons may contribute to PFC dysfunction. To identify how PVIs contribute to PFC-dependent behaviors we inactivated PVIs in the PFC in mice using region- and cell-type-selective expression of tetanus toxin light chain (TeLC) and compared the functional consequences of this manipulation with non-cell-type-selective perturbations of the same circuitry. By sampling for behavioral alterations that map onto distinct symptom categories in schizophrenia, we show that dysfunction of PVI signaling in the PFC specifically produces deficits in the cognitive domain, but does not give rise to PFC-dependent correlates of negative or positive symptoms. Our results suggest that distinct aspects of the complex symptomatology of PFC dysfunction in schizophrenia can be attributed to specific prefrontal circuit elements.
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.|Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murray
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.
authors.forename: Marta U
authors.initials: MU
authors.lastname: Woloszynowska-Fraser
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.|Institute of Physiology, Christian Albrechts University Kiel, 24098 Kiel, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Ansel-Bollepalli
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.
authors.forename: Katy L H
authors.initials: KL
authors.lastname: Cole
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.|Institute of Physiology, Christian Albrechts University Kiel, 24098 Kiel, Germany.
authors.forename: Angelica
authors.initials: A
authors.lastname: Foggetti
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.
authors.forename: Barry
authors.initials: B
authors.lastname: Crouch
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.
authors.forename: Gernot
authors.initials: G
authors.lastname: Riedel
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.|Institute of Physiology, Christian Albrechts University Kiel, 24098 Kiel, Germany.
authors.forename: Peer
authors.initials: P
authors.lastname: Wulff
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D005260:Female; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008666:Metalloendopeptidases / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects; D012919:Social Behavior; D009435:Synaptic Transmission / Q000187:drug effects; D013744:Tetanus Toxin / Q000378:metabolism
chemical_list: D010320:Parvalbumins; D013744:Tetanus Toxin; D000661:Amphetamine; D008666:Metalloendopeptidases; C093556:zinc-endopeptidase, tetanus neurotoxin