Control of impulsivity by G
| Autor: | Bastiaan, van der Veen, Sampath K T, Kapanaiah, Kasyoka, Kilonzo, Peter, Steele-Perkins, Martin M, Jendryka, Stefanie, Schulz, Bosiljka, Tasic, Zizhen, Yao, Hongkui, Zeng, Thomas, Akam, Janet R, Nicholson, Birgit, Liss, Wiebke, Nissen, Anton, Pekcec, Dennis, Kätzel |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Mice Knockout Pyramidal Cells Gene Expression Mice Transgenic GTP-Binding Protein alpha Subunits Gi-Go Receptors Metabotropic Glutamate Gyrus Cinguli Neural circuits Article Mice Inbred C57BL Mice Target identification Impulsive Behavior Cognitive control Animals Humans Diseases of the nervous system Female Clozapine Signal Transduction |
| Zdroj: | Communications Biology |
| ISSN: | 2399-3642 |
| Popis: | Pathological impulsivity is a debilitating symptom of multiple psychiatric diseases with few effective treatment options. To identify druggable receptors with anti-impulsive action we developed a systematic target discovery approach combining behavioural chemogenetics and gene expression analysis. Spatially restricted inhibition of three subdivisions of the prefrontal cortex of mice revealed that the anterior cingulate cortex (ACC) regulates premature responding, a form of motor impulsivity. Probing three G-protein cascades with designer receptors, we found that the activation of Gi-signalling in layer-5 pyramidal cells (L5-PCs) of the ACC strongly, reproducibly, and selectively decreased challenge-induced impulsivity. Differential gene expression analysis across murine ACC cell-types and 402 GPCRs revealed that - among Gi-coupled receptor-encoding genes - Grm2 is the most selectively expressed in L5-PCs while alternative targets were scarce. Validating our approach, we confirmed that mGluR2 activation reduced premature responding. These results suggest Gi-coupled receptors in ACC L5-PCs as therapeutic targets for impulse control disorders. In order to identify receptors that may serve as therapeutic targets in the treatment of impulse control disorders, van der Veen et al developed a systematic target discovery approach combining behavioural chemogenetics and gene expression analysis. In doing so, they identified Gi-coupled receptors in layer-5 pyramidal cells of the anterior cingulate cortex as potential therapeutic targets, which could pave the way for the development of treatments. |
| Databáze: | OpenAIRE |
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