Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility

Andrew J. Murray, Marta U. Woloszynowska-Fraser, Laura Ansel-Bollepalli, Katy L. H. Cole, Angelica Foggetti, Barry Crouch, Gernot Riedel (Corresponding Author), Peer Wulff (Corresponding Author)

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number16778
Number of pages14
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 26 Nov 2015

Keywords

  • GENE-EXPRESSION
  • SPATIAL MEMORY
  • IBOTENIC ACID
  • SCHIZOPHRENIA
  • NEURONS
  • HIPPOCAMPAL
  • MICE
  • DYSFUNCTION
  • RATS
  • DOPAMINE

Cite this

Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility. / Murray, Andrew J.; Woloszynowska-Fraser, Marta U.; Ansel-Bollepalli, Laura; Cole, Katy L. H.; Foggetti, Angelica; Crouch, Barry; Riedel, Gernot (Corresponding Author); Wulff, Peer (Corresponding Author).

In: Scientific Reports, Vol. 5, 16778, 26.11.2015.

Research output: Contribution to journalArticle

Murray, Andrew J. ; Woloszynowska-Fraser, Marta U. ; Ansel-Bollepalli, Laura ; Cole, Katy L. H. ; Foggetti, Angelica ; Crouch, Barry ; Riedel, Gernot ; Wulff, Peer. / Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility. In: Scientific Reports. 2015 ; Vol. 5.
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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.",
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