Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys
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.
Article and author information
Author details
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.
Reviewing Editor
- Rui M Costa, Fundação Champalimaud, Portugal
Version history
- Received: March 29, 2016
- Accepted: August 22, 2016
- Accepted Manuscript published: August 23, 2016 (version 1)
- Version of Record published: September 20, 2016 (version 2)
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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Further reading
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- Genetics and Genomics
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In the fruit fly Drosophila melanogaster, gustatory sensory neurons express taste receptors that are tuned to distinct groups of chemicals, thereby activating neural ensembles that elicit either feeding or avoidance behavior. Members of a family of ligand -gated receptor channels, the Gustatory receptors (Grs), play a central role in these behaviors. In general, closely related, evolutionarily conserved Gr proteins are co-expressed in the same type of taste neurons, tuned to chemically related compounds, and therefore triggering the same behavioral response. Here, we report that members of the Gr28 subfamily are expressed in largely non-overlapping sets of taste neurons in Drosophila larvae, detect chemicals of different valence, and trigger opposing feeding behaviors. We determined the intrinsic properties of Gr28 neurons by expressing the mammalian Vanilloid Receptor 1 (VR1), which is activated by capsaicin, a chemical to which wild-type Drosophila larvae do not respond. When VR1 is expressed in Gr28a neurons, larvae become attracted to capsaicin, consistent with reports showing that Gr28a itself encodes a receptor for nutritious RNA. In contrast, expression of VR1 in two pairs of Gr28b.c neurons triggers avoidance to capsaicin. Moreover, neuronal inactivation experiments show that the Gr28b.c neurons are necessary for avoidance of several bitter compounds. Lastly, behavioral experiments of Gr28 deficient larvae and live Ca2+ imaging studies of Gr28b.c neurons revealed that denatonium benzoate, a synthetic bitter compound that shares structural similarities with natural bitter chemicals, is a ligand for a receptor complex containing a Gr28b.c or Gr28b.a subunit. Thus, the Gr28 proteins, which have been evolutionarily conserved over 260 million years in insects, represent the first taste receptor subfamily in which specific members mediate behavior with opposite valence.