Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4
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 remains largely unknown. Here, by combining a Go/No-Go behavioral assay with resting-state (...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/62123 |
| _version_ | 1818026457166774272 |
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| author | Lukasz Piszczek Andreea Constantinescu Dominic Kargl Jelena Lazovic Anton Pekcec Janet R Nicholson Wulf Haubensak |
| author_facet | Lukasz Piszczek Andreea Constantinescu Dominic Kargl Jelena Lazovic Anton Pekcec Janet R Nicholson Wulf Haubensak |
| author_sort | Lukasz Piszczek |
| collection | DOAJ |
| description | 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 remains 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 hotspot 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 bidirectionally 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. |
| first_indexed | 2024-12-10T04:32:18Z |
| format | Article |
| id | doaj.art-6fd0b3a2a2f346bfa90ac9fa3a32584a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:32:18Z |
| publishDate | 2022-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6fd0b3a2a2f346bfa90ac9fa3a32584a2022-12-22T02:02:07ZengeLife Sciences Publications LtdeLife2050-084X2022-01-011110.7554/eLife.62123Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4Lukasz Piszczek0https://orcid.org/0000-0003-2017-8853Andreea Constantinescu1https://orcid.org/0000-0002-3081-0755Dominic Kargl2https://orcid.org/0000-0001-7206-1708Jelena Lazovic3Anton Pekcec4Janet R Nicholson5Wulf Haubensak6https://orcid.org/0000-0002-2034-9184The Research Institute of Molecular Pathology (IMP), Department of Neuroscience, Vienna Biocenter, Vienna, AustriaThe Research Institute of Molecular Pathology (IMP), Department of Neuroscience, Vienna Biocenter, Vienna, AustriaThe Research Institute of Molecular Pathology (IMP), Department of Neuroscience, Vienna Biocenter, Vienna, Austria; Department of Neuronal Cell Biology, Center for Brain Research, Medical University of Vienna, Vienna, AustriaPreclinical Imaging Facility, Vienna BioCenter Core Facilities (VBCF), Vienna, AustriaDiv Research Germany, Boehringer Ingelheim, Biberach an der Riss, GermanyDiv Research Germany, Boehringer Ingelheim, Biberach an der Riss, GermanyThe Research Institute of Molecular Pathology (IMP), Department of Neuroscience, Vienna Biocenter, Vienna, Austria; Department of Neuronal Cell Biology, Center for Brain Research, Medical University of Vienna, Vienna, AustriaBehavioral 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 remains 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 hotspot 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 bidirectionally 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.https://elifesciences.org/articles/62123behavioral traitGo/No-Go taskfMRImGlu4STNimpulsivity |
| spellingShingle | Lukasz Piszczek Andreea Constantinescu Dominic Kargl Jelena Lazovic Anton Pekcec Janet R Nicholson Wulf Haubensak Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4 eLife behavioral trait Go/No-Go task fMRI mGlu4 STN impulsivity |
| title | Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4 |
| title_full | Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4 |
| title_fullStr | Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4 |
| title_full_unstemmed | Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4 |
| title_short | Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4 |
| title_sort | dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4 |
| topic | behavioral trait Go/No-Go task fMRI mGlu4 STN impulsivity |
| url | https://elifesciences.org/articles/62123 |
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