Ruud, Johan, Alber, Jens, Tokarska, Anna ORCID: 0000-0001-9734-2354, Ruud, Linda Engstroem, Nolte, Hendrik, Biglari, Nasim, Lippert, Rachel ORCID: 0000-0002-6905-2234, Lautenschlager, Anne, Ciealak, Przemyslaw E., Szumiec, Lukasz, Hess, Martin E., Broenneke, Hella S., Krueger, Marcus, Nissbrandt, Hans, Korotkova, Tatiana, Silberberg, Gilad ORCID: 0000-0001-9964-505X, Parkitna, Jan Rodriguez and Bruening, Jens C. (2019). The Fat Mass and Obesity-Associated Protein (FTO) Regulates Locomotor Responses to Novelty via D2R Medium Spiny Neurons. Cell Reports, 27 (11). S. 3182 - 3208. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Variations in the human FTO gene have been linked to obesity and altered connectivity of the dopaminergic neurocircuitry. Here, we report that fat mass and obesity-associated protein (FTO) in dopamine D2 receptor-expressing medium spiny neurons (D2 MSNs) of mice regulate the excitability of these cells and control their striatopallidal globus pallidus external (GPe) projections. Lack of FTO in D2 MSNs translates into increased locomotor activity to novelty, associated with altered timing behavior, without impairing the ability to control actions or affecting reward-driven and conditioned behavior. Pharmacological manipulations of dopamine D1 receptor (D1R)- or D2R-dependent pathways in these animals reveal altered responses to D1- and D2-MSN-mediated control of motor output. These findings reveal a critical role for FTO to control D2 MSN excitability, their projections to the GPe, and behavioral responses to novelty.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ruud, JohanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alber, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tokarska, AnnaUNSPECIFIEDorcid.org/0000-0001-9734-2354UNSPECIFIED
Ruud, Linda EngstroemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Biglari, NasimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lippert, RachelUNSPECIFIEDorcid.org/0000-0002-6905-2234UNSPECIFIED
Lautenschlager, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ciealak, Przemyslaw E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szumiec, LukaszUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hess, Martin E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Broenneke, Hella S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nissbrandt, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korotkova, TatianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Silberberg, GiladUNSPECIFIEDorcid.org/0000-0001-9964-505XUNSPECIFIED
Parkitna, Jan RodriguezUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-137915
DOI: 10.1016/j.celrep.2019.05.037
Journal or Publication Title: Cell Reports
Volume: 27
Number: 11
Page Range: S. 3182 - 3208
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENE-EXPRESSION; NEURAL MECHANISMS; MICE; RNA; VARIANT; INTERNEURONS; METHYLATION; IMPULSIVITY; IDENTIFICATION; ENRICHMENTMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13791

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