Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
| Autor: | Aparna Rajagopalan, Souha Mahmoudi, Casey J. A. Smith-Anttila, Sylvie Dumas, Stefano Pupe, Nadine Schweizer, Daniel Lévesque, Anna Andrén, Karin Nordenankar, Richardson N. Leão, Emma Arvidsson, Åsa Wallén-Mackenzie |
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| Rok vydání: | 2014 |
| Předmět: |
striatum
Dopamine Population Glutamic Acid Striatum Hyperkinesis Synaptic Transmission Glutamatergic Mice Subthalamic Nucleus vesicular transporter Basal ganglia medicine Animals Letters optogenetics education Maze Learning In Situ Hybridization Dopamine transporter Homeodomain Proteins Mice Knockout education.field_of_study Multidisciplinary biology Reverse Transcriptase Polymerase Chain Reaction Dopaminergic Excitatory Postsynaptic Potentials Biological Sciences Immunohistochemistry deep brain stimulation Parkinson disease Subthalamic nucleus surgical procedures operative nervous system biology.protein Vesicular Glutamate Transport Protein 2 Neuroscience medicine.drug Transcription Factors |
| Zdroj: | Repositório Institucional da UFRN Universidade Federal do Rio Grande do Norte (UFRN) instacron:UFRN |
| ISSN: | 1091-6490 |
| Popis: | The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knock-out mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects. |
| Databáze: | OpenAIRE |
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