Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4
- Vienna Biocenter, Austria
- Vienna BioCenter Core Facilities (VBCF), Austria
- Boehringer Ingelheim, Germany
Abstract
Behavioral strategies require gating of premature responses to optimize outcomes. Several brain areas control impulsive actions, but the neuronal basis of natural variation in impulsivity between individuals remain largely unknown. Here, by combining a Go/No-Go behavioral assay with resting state (rs) functional MRI in mice, we identified the subthalamic nucleus (STN), a known gate for motor control in the basal ganglia, as a major hot spot for trait impulsivity. In vivo recorded STN neural activity encoded impulsive action as a separable state from basic motor control, characterized by decoupled STN/Substantia nigra pars reticulata (SNr) mesoscale networks. Optogenetic modulation of STN activity bi-directionally controlled impulsive behavior. Pharmacological and genetic manipulations showed that these impulsive actions are modulated by metabotropic glutamate receptor 4 (mGlu4) function in STN and its coupling to SNr in a behavioral trait-dependent manner, and independently of general motor function. In conclusion, STN circuitry multiplexes motor control and trait impulsivity, which are molecularly dissociated by mGlu4. This provides a potential mechanism for the genetic modulation of impulsive behavior, a clinically relevant predictor for developing psychiatric disorders associated with impulsivity.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
H2020 European Research Council (311701)
- Wulf Haubensak
Boehringer Ingelheim
- Wulf Haubensak
Österreichische Forschungsförderungsgesellschaft
- Wulf Haubensak
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal procedures were performed in accordance with institutional guidelines and were approved by the 4 respective Austrian (BGBl nr. 501/1988, idF BGBl I no. 162/2005) and European authorities (Directive 86/609/EEC of 24 November 1986, European Community) and covered by the license M58/002220/2011/9.
Copyright
© 2022, Piszczek et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4
eLife 11:e62123.
https://doi.org/10.7554/eLife.62123
