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; Peer Wulff

doi:10.1038/srep16778

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)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

107 Citations (Scopus)

14 Downloads (Pure)

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 language	English
Article number	16778
Number of pages	14
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep16778
Publication status	Published - 26 Nov 2015

Bibliographical note

We were supported by the Biotechnology and Biological Sciences Research Council grant BB/H001123/1 (P.W.), the Medical Research Council grants G0601498 and G1100546/2 (P.W.), Tenovus Scotland Grant G09/17 (A.J.M.) and the University of Aberdeen (P.W.). We thank O. Tüscher for discussion, P. Teismann and the microscopy core facility at the University of Aberdeen for the use of microscopy equipment, L. Strachan, A. Plano, S. Deiana for help with behavioral testing.

Keywords

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

Access to Document

10.1038/srep16778Licence: CC BY

Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Final published version, 1.92 MBLicence: CC BY

Gernot Riedel
Person: Academic

Cite this

@article{edd2ae42fba74c5086e6d0087b67d316,

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.",

keywords = "GENE-EXPRESSION, SPATIAL MEMORY, IBOTENIC ACID, SCHIZOPHRENIA, NEURONS, HIPPOCAMPAL, MICE, DYSFUNCTION, RATS, DOPAMINE",

author = "Murray, {Andrew J.} and Woloszynowska-Fraser, {Marta U.} and Laura Ansel-Bollepalli and Cole, {Katy L. H.} and Angelica Foggetti and Barry Crouch and Gernot Riedel and Peer Wulff",

note = "We were supported by the Biotechnology and Biological Sciences Research Council grant BB/H001123/1 (P.W.), the Medical Research Council grants G0601498 and G1100546/2 (P.W.), Tenovus Scotland Grant G09/17 (A.J.M.) and the University of Aberdeen (P.W.). We thank O. T{\"u}scher for discussion, P. Teismann and the microscopy core facility at the University of Aberdeen for the use of microscopy equipment, L. Strachan, A. Plano, S. Deiana for help with behavioral testing.",

year = "2015",

month = nov,

day = "26",

doi = "10.1038/srep16778",

language = "English",

volume = "5",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility

AU - Murray, Andrew J.

AU - Woloszynowska-Fraser, Marta U.

AU - Ansel-Bollepalli, Laura

AU - Cole, Katy L. H.

AU - Foggetti, Angelica

AU - Crouch, Barry

AU - Riedel, Gernot

AU - Wulff, Peer

N1 - We were supported by the Biotechnology and Biological Sciences Research Council grant BB/H001123/1 (P.W.), the Medical Research Council grants G0601498 and G1100546/2 (P.W.), Tenovus Scotland Grant G09/17 (A.J.M.) and the University of Aberdeen (P.W.). We thank O. Tüscher for discussion, P. Teismann and the microscopy core facility at the University of Aberdeen for the use of microscopy equipment, L. Strachan, A. Plano, S. Deiana for help with behavioral testing.

PY - 2015/11/26

Y1 - 2015/11/26

N2 - 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.

AB - 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.

KW - GENE-EXPRESSION

KW - SPATIAL MEMORY

KW - IBOTENIC ACID

KW - SCHIZOPHRENIA

KW - NEURONS

KW - HIPPOCAMPAL

KW - MICE

KW - DYSFUNCTION

KW - RATS

KW - DOPAMINE

U2 - 10.1038/srep16778

DO - 10.1038/srep16778

M3 - Article

SN - 2045-2322

VL - 5

JO - Scientific Reports

JF - Scientific Reports

M1 - 16778

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Profiles

Gernot Riedel

Cite this