Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys
- The Hebrew University-Hadassah Medical School, Israel
- University of Rochester School of Medicine, United States
- Hadassah University Hospital, Israel
Abstract
The striatum and the subthalamic nucleus (STN) constitute the input stage of the basal ganglia (BG) network and together innervate BG downstream structures using GABA and glutamate, respectively. Comparison of the neuronal activity in BG input and downstream structures reveals that subthalamic, not striatal, activity fluctuations correlate with modulations in the increase/decrease discharge balance of BG downstream neurons during temporal discounting classical condition task. After induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), abnormal low beta (8-15 Hz) spiking and local field potential (LFP) oscillations resonate across the BG network. Nevertheless, LFP beta oscillations entrain spiking activity of STN, striatal cholinergic interneurons and BG downstream structures, but do not entrain spiking activity of striatal projection neurons. Our results highlight the pivotal role of STN divergent projections in BG physiology and pathophysiology and may explain why STN is such an effective site for invasive treatment of advanced Parkinson's disease and other BG-related disorders.
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Funding
The Edmond and Lily Safra Center
- Marc Deffains
- Liliya Iskhakova
The Rosetrees and Vorst Foundations (ROSETREES 251112 and ROSETREES TRUST 271010)
- Hagai Bergman
The Simone and Bernard Guttman Chair in Brain Research
- Hagai Bergman
Ministry of Aliyah and Immigrant Absorption
- Liliya Iskhakova
The Teva National Network of Excellence in Neuroscience
- Liliya Iskhakova
The Israel-US Binational Science Foundation
- Suzanne N Haber
- Zvi Israel
- Hagai Bergman
The Adelis Foundation
- Suzanne N Haber
- Zvi Israel
- Hagai Bergman
European Research Council (GA 322495 CLUE-BGD 098777)
- Hagai Bergman
Israel Science Foundation
- Hagai Bergman
The German Israel Science Foundation (I-1222-377.13/2010 002223)
- Hagai Bergman
The Canadian Friends of the Hebrew University
- Hagai Bergman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental protocols were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and with the Hebrew University guidelines for the use and care of laboratory animals in research, supervised by the institutional animal care and use committee of the faculty of medicine, the Hebrew University, Jerusalem, Israel (Ethical Application Reference Number: MD-15-14412-5 ). The Hebrew University is an Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) internationally accredited institute.
Copyright
© 2016, Deffains 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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Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys
eLife 5:e16443.
https://doi.org/10.7554/eLife.16443
