1. Neuroscience
Download icon

Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys

  1. Marc Deffains  Is a corresponding author
  2. Liliya Iskhakova
  3. Shiran Katabi
  4. Suzanne N Haber
  5. Zvi Israel
  6. Hagai Bergman
  1. The Hebrew University-Hadassah Medical School, Israel
  2. University of Rochester School of Medicine, United States
  3. Hadassah University Hospital, Israel
Research Article
  • Cited 56
  • Views 3,002
  • Annotations
Cite this article as: eLife 2016;5:e16443 doi: 10.7554/eLife.16443

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

  1. Marc Deffains

    Department of Medical Neurobiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
    For correspondence
    marcd@ekmd.huji.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0734-6541
  2. Liliya Iskhakova

    Department of Medical Neurobiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Shiran Katabi

    Department of Medical Neurobiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Suzanne N Haber

    Department of Pharmacology and Physiology, University of Rochester School of Medicine, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Zvi Israel

    Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Hagai Bergman

    Department of Medical Neurobiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2402-6673

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

  1. Rui M Costa, Fundação Champalimaud, Portugal

Publication history

  1. Received: March 29, 2016
  2. Accepted: August 22, 2016
  3. Accepted Manuscript published: August 23, 2016 (version 1)
  4. 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.

Metrics

  • 3,002
    Page views
  • 666
    Downloads
  • 56
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Christian Brodbeck et al.
    Research Article

    Speech processing is highly incremental. It is widely accepted that human listeners continuously use the linguistic context to anticipate upcoming concepts, words, and phonemes. However, previous evidence supports two seemingly contradictory models of how a predictive context is integrated with the bottom-up sensory input: Classic psycholinguistic paradigms suggest a two-stage process, in which acoustic input initially leads to local, context-independent representations, which are then quickly integrated with contextual constraints. This contrasts with the view that the brain constructs a single coherent, unified interpretation of the input, which fully integrates available information across representational hierarchies, and thus uses contextual constraints to modulate even the earliest sensory representations. To distinguish these hypotheses, we tested magnetoencephalography responses to continuous narrative speech for signatures of local and unified predictive models. Results provide evidence that listeners employ both types of models in parallel. Two local context models uniquely predict some part of early neural responses, one based on sublexical phoneme sequences, and one based on the phonemes in the current word alone; at the same time, even early responses to phonemes also reflect a unified model that incorporates sentence level constraints to predict upcoming phonemes. Neural source localization places the anatomical origins of the different predictive models in non-identical parts of the superior temporal lobes bilaterally, with the right hemisphere showing a relative preference for more local models. These results suggest that speech processing recruits both local and unified predictive models in parallel, reconciling previous disparate findings. Parallel models might make the perceptual system more robust, facilitate processing of unexpected inputs, and serve a function in language acquisition.

    1. Neuroscience
    Travis A Hage et al.
    Research Article

    Understanding cortical microcircuits requires thorough measurement of physiological properties of synaptic connections formed within and between diverse subclasses of neurons. Towards this goal, we combined spatially precise optogenetic stimulation with multicellular recording to deeply characterize intralaminar and translaminar monosynaptic connections to supragranular (L2/3) neurons in the mouse visual cortex. The reliability and specificity of multiphoton optogenetic stimulation were measured across multiple Cre lines and measurements of connectivity were verified by comparison to paired recordings and targeted patching of optically identified presynaptic cells. With a focus on translaminar pathways, excitatory and inhibitory synaptic connections from genetically defined presynaptic populations were characterized by their relative abundance, spatial profiles, strength, and short-term dynamics. Consistent with the canonical cortical microcircuit, layer 4 excitatory neurons and interneurons within L2/3 represented the most common sources of input to L2/3 pyramidal cells. More surprisingly, we also observed strong excitatory connections from layer 5 intratelencephalic neurons and potent translaminar inhibition from multiple interneuron subclasses. The hybrid approach revealed convergence to and divergence from excitatory and inhibitory neurons within and across cortical layers. Divergent excitatory connections often spanned hundreds of microns of horizontal space. In contrast, divergent inhibitory connections were more frequently measured from postsynaptic targets near each other.