Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
2014 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 21, 7837-7842 p.Article in journal (Refereed) Published
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 knockout 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.
Place, publisher, year, edition, pages
2014. Vol. 111, no 21, 7837-7842 p.
Parkinson disease, deep brain stimulation, vesicular transporter, optogenetics, striatum
IdentifiersURN: urn:nbn:se:uu:diva-227717DOI: 10.1073/pnas.1323499111ISI: 000336411300073OAI: oai:DiVA.org:uu-227717DiVA: diva2:731042
N.S. and S.P. contributed equally to this work.2014-06-302014-06-302016-05-11Bibliographically approved