Uniting functional network topology and oscillations in the fronto-parietal single unit network of behaving primates

  1. Benjamin Dann
  2. Jonathan A Michaels
  3. Stefan Schaffelhofer
  4. Hansjörg Scherberger  Is a corresponding author
  1. German Primate Center, Germany
  2. German Primate Center GmbH, Germany

Abstract

The functional communication of neurons in cortical networks underlies higher cognitive processes. Yet, little is known about the organization of the single neuron network or its relationship to the synchronization processes that are essential for its formation. Here, we show that the functional single neuron network of three fronto-parietal areas during active behavior of macaque monkeys is highly complex. The network was closely connected (small-world) and consisted of functional modules spanning these areas. Surprisingly, the importance of different neurons to the network was highly heterogeneous with a small number of neurons contributing strongly to the network function (hubs), which were in turn strongly inter-connected (rich-club). Examination of the network synchronization revealed that the identified rich-club consisted of neurons that were synchronized in the beta or low frequency range, whereas other neurons were mostly non-oscillatory synchronized. Therefore, oscillatory synchrony may be a central communication mechanism for highly organized functional spiking networks.

Article and author information

Author details

  1. Benjamin Dann

    Neurobiology Laboratory, German Primate Center, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Jonathan A Michaels

    Neurobiology Laboratory, German Primate Center, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5179-3181
  3. Stefan Schaffelhofer

    Neurobiology Lab, German Primate Center GmbH, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1006-971X
  4. Hansjörg Scherberger

    Neurobiology Lab, German Primate Center GmbH, Göttingen, Germany
    For correspondence
    hscherb@gwdg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6593-2800

Funding

Deutsche Forschungsgemeinschaft (SCHE 1575/1-1 & 3-1 and SFB889, C9)

  • Hansjörg Scherberger

European Commission (FP7-611687, NEBIAS)

  • Hansjörg Scherberger

Bundesministerium für Bildung und Forschung (BCCN-II, 01GQ1005C)

  • Hansjörg Scherberger

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 procedures and animal care were conducted in accordance with the guidelines for the care and use of mammals in neuroscience and behavioral research (National Research Council, 2003), and were in agreement with German and European laws governing animal care. Authorization for conducting this study has been granted by the regional government office, the Animal Welfare Division of the Office for Consumer Protection and Food Safety of the State of Lower Saxony, Germany (permit no. 032/09). Monkey handling also followed the recommendations of the Weatherall Report of good animal practice. Animals were pairhoused in a spacious cage (well exceeding legal requirements) and were maintained on a 12-hour on/off lighting schedule. Housing procedures included an environmental enrichment program with access to toys, swings, and hidden treats (e.g., seeds in sawdust). Monkeys had visual and auditory contact to other monkeys. They were fed on a diet of enriched biscuits and fruits. Daily access to fluids was controlled during training and experimental periods to promote behavioral motivation. All surgical procedures were performed under anesthesia, and all efforts were made to minimize post-surgical pain or suffering. Institutional veterinarians continually monitored animal health and well-being.

Copyright

© 2016, Dann 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

  • 3,553
    views
  • 750
    downloads
  • 61
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

Share this article

https://doi.org/10.7554/eLife.15719

Further reading

    1. Neuroscience
    Gergely F Turi, Sasa Teng ... Yueqing Peng
    Research Article

    Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.

    1. Neuroscience
    Ulrike Pech, Jasper Janssens ... Patrik Verstreken
    Research Article

    The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson’s disease patients confirms these findings. Indeed, the disturbances lead to early synaptic dysfunction, notably affecting cholinergic olfactory projection neurons crucial for olfactory function in flies. Correcting these defects specifically in olfactory cholinergic interneurons in flies or inducing cholinergic signaling in Parkinson mutant human induced dopaminergic neurons in vitro using nicotine, both rescue age-dependent dopaminergic neuron decline. Hence, our research uncovers that one of the earliest indicators of disease in five different models of familial Parkinsonism is synaptic dysfunction in higher-order cholinergic projection neurons and this contributes to the development of hyposmia. Furthermore, the shared pathways of synaptic failure in these cholinergic neurons ultimately contribute to dopaminergic dysfunction later in life.