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The Fat Mass and Obesity-Associated Protein (FTO) Regulates Locomotor Responses to Novelty via D2R Medium Spiny Neurons.
- Source :
-
Cell reports [Cell Rep] 2019 Jun 11; Vol. 27 (11), pp. 3182-3198.e9. - Publication Year :
- 2019
-
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.<br /> (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Action Potentials
Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics
Animals
Dopaminergic Neurons physiology
Female
Globus Pallidus cytology
Globus Pallidus metabolism
Globus Pallidus physiology
Male
Mice
Receptors, Dopamine D1 genetics
Receptors, Dopamine D1 metabolism
Receptors, Dopamine D2 genetics
Receptors, Dopamine D2 metabolism
Reward
Alpha-Ketoglutarate-Dependent Dioxygenase FTO metabolism
Dopaminergic Neurons metabolism
Exploratory Behavior
Locomotion
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 27
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 31189104
- Full Text :
- https://doi.org/10.1016/j.celrep.2019.05.037