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  On the role of arkypallidal and prototypical neurons for phase transitions in the external pallidum

Gast, R., Gong, R., Schmidt, H., Meijer, H. G., & Knösche, T. R. (2021). On the role of arkypallidal and prototypical neurons for phase transitions in the external pallidum. The Journal of Neuroscience, 41(31), 6673-6683. doi:10.1523/JNEUROSCI.0094-21.2021.

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 Creators:
Gast, Richard1, Author              
Gong, Ruxue1, Author              
Schmidt, Helmut1, Author              
Meijer, Hil G.E.2, Author
Knösche, Thomas R.1, 3, Author              
Affiliations:
1Methods and Development Group Brain Networks, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_2205650              
2Department of Applied Mathematics, Technical Medical Centre (TechMed),, ou_persistent22              
3Institute for Biomedical Engineering and Informatics, TU Ilmenau, Germany, ou_persistent22              

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Free keywords: Parkinson; Basal ganglia; Neural network; Oscillations; Pallidum; Phase-amplitude coupling
 Abstract: The external pallidum (globus pallidus pars externa [GPe]) plays a central role for basal ganglia functions and dynamics and, consequently, has been included in most computational studies of the basal ganglia. These studies considered the GPe as a homogeneous neural population. However, experimental studies have shown that the GPe contains at least two distinct cell types (prototypical and arkypallidal cells). In this work, we provide in silico insight into how pallidal heterogeneity modulates dynamic regimes inside the GPe and how they affect the GPe response to oscillatory input. We derive a mean-field model of the GPe system from a microscopic spiking neural network of recurrently coupled prototypical and arkypallidal neurons. Using bifurcation analysis, we examine the influence of dopamine-dependent changes of intrapallidal connectivity on the GPe dynamics. We find that increased self-inhibition of prototypical cells can induce oscillations, whereas increased inhibition of prototypical cells by arkypallidal cells leads to the emergence of a bistable regime. Furthermore, we show that oscillatory input to the GPe, arriving from striatum, leads to characteristic patterns of cross-frequency coupling observed at the GPe. Based on these findings, we propose two different hypotheses of how dopamine depletion at the GPe may lead to phase-amplitude coupling between the parkinsonian beta rhythm and a GPe-intrinsic γ rhythm. Finally, we show that these findings generalize to realistic spiking neural networks of sparsely coupled Type I excitable GPe neurons.SIGNIFICANCE STATEMENT Our work provides (1) insight into the theoretical implications of a dichotomous globus pallidus pars externa (GPe) organization, and (2) an exact mean-field model that allows for future investigations of the relationship between GPe spiking activity and local field potential fluctuations. We identify the major phase transitions that the GPe can undergo when subject to static or periodic input and link these phase transitions to the emergence of synchronized oscillations and cross-frequency coupling in the basal ganglia. Because of the close links between our model and experimental findings on the structure and dynamics of prototypical and arkypallidal cells, our results can be used to guide both experimental and computational studies on the role of the GPe for basal ganglia dynamics in health and disease.

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Language(s): eng - English
 Dates: 2021-04-082021-01-152021-05-132021-06-302021-08-04
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1523/JNEUROSCI.0094-21.2021
Other: epub 2021
PMID: 34193559
PMC: PMC8336705
 Degree: -

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Title: The Journal of Neuroscience
  Other : The Journal of Neuroscience: the Official Journal of the Society for Neuroscience
  Abbreviation : J. Neurosci.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Washington, DC : Society of Neuroscience
Pages: - Volume / Issue: 41 (31) Sequence Number: - Start / End Page: 6673 - 6683 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187_1