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@INPROCEEDINGS{Bahuguna:829370,
author = {Bahuguna, Jyotika and Tetzlaff, Tom and Arvind, Kumar and
Kotaleski, Jeanette Hellgren and Morrison, Abigail},
title = {{H}omologous basal-ganglia networks in physiological and
parkinsonian conditions},
reportid = {FZJ-2017-03085},
year = {2017},
abstract = {The classical model of basal ganglia (BG) has been
regularly updated with discoveries of new sub-populations
within a nucleus or new projections from existing nuclei in
recent years. It is unclear how these new insights on the
structure of the BG network foster our understanding of its
function. The effective connectivities among these recently
identified BG sub-populations are only partially known. In
the framework of a simple firing-rate model subjected to a
genetic algorithm, we identified effective BG connectivities
which are consistent with experimentally established
firing-rate and phase relationships in Subthalamic Nucleus
(STN) and two GPe subpopulations (arkypallidal [GPe-TA] and
prototypical [GPe -TI]) in both healthy and PD states
[1].Firstly, we found that multiple parameter combinations
can fit the data. We functionally re-classified these PD and
healthy network models on the basis of two dynamical
features: suppression of GPi activity and susceptibility of
the BG network to oscillate in the presence of cortical
input. These features were chosen because task execution
requires GPi suppression while oscillations in the STN-GPe
subnetwork are characteristic of PD. We found that most
putative pathological networks showed insufficient
suppression of GPi activity and high susceptibility to
oscillations whereas most putative healthy networks showed
sufficient suppression of GPi activity and low
susceptibility to oscillations. This is consistent with
experimental data that shows that lack of GPi suppression
[2] or oscillations [3,4] is correlated with Parkinsonian
symptoms such as stymied movement and tremor. A small
fraction of networks, however, in both cases show deficiency
in only one of the features. This could indicate the
configurations of healthy networks that might be more
pathology prone and in contrast configurations of
pathological networks that might be easier to push into a
healthy state. Further analysis of estimated BG connectivity
revealed that transitions between the putative PD and
healthy networks were possible by modifying the strength of
the relevant projections. Most of the transitions involved
changes in corticostriatal, striatopallidal and
pallidopallidal projections. Finally, the variance observed
in the functional classification of putative pathological
and healthy networks might hint at the variance observed in
manifestation of Parkinson's disease
(PD).AcknowledgementsKlinische Forschergruppe (KFO219, TP12)
of the Deutsche Forschungsgemeinschaft; Helmholtz
Association, EuroSPIN and Erasmus Mundus Joint Doctorate
Programme.References1.Abdi A, Mallet N, Mohamed FY, Sharott
A, Dodson PD, Nakamura KC, Suri S, Avery SV, Larvin JT,
Garas FN, Garas SN, Vinciati F, Morin S, Bezard E, Baufreton
J, Magill PJ: Prototypic and Arkypallidal Neurons in the
Dopamine-Intact External Globus Pallidus . J Neurosci 2015,
37(17): 6667-6688.2. Boraud T, Bezard E, Bioulac B, Gross
CE: Ratio of inhibited-to-activated pallidal neurons
decreases dramatically during passive limb movement in the
MPTP-treated monkey. J. Physiol 2000, 83(3): 1760-1763. 3.
Chen CC, Litvak V, Gilbertson T, Kühn A, Lu CS, Lee ST,
Tsai CH, Tisch S, Limousin P, Hariz M, Brown P: Excessive
synchronization of basal ganglia neurons at 20 Hz slows
movement in Parkinson's disease. Exp Neurol. 2007, 205(1):
214-221.4. Moran A, Bergman H, Israel Z, Bar-Gad I:
Subthalamic nucleus functional organization revealed by
parkinsonian neuronal oscillations and synchrony. Brain
2008, 131(Pt-12): 3395-3409.},
month = {Mar},
date = {2017-03-24},
organization = {12th International Basal Ganglia
Society Meeting, Merida (Mexico), 24
Mar 2017 - 31 Mar 2017},
subtyp = {After Call},
cin = {INM-6 / IAS-6 / INM-10},
cid = {I:(DE-Juel1)INM-6-20090406 / I:(DE-Juel1)IAS-6-20130828 /
I:(DE-Juel1)INM-10-20170113},
pnm = {574 - Theory, modelling and simulation (POF3-574) / 571 -
Connectivity and Activity (POF3-571) / 331 - Signalling
Pathways and Mechanisms in the Nervous System (POF2-331)},
pid = {G:(DE-HGF)POF3-574 / G:(DE-HGF)POF3-571 /
G:(DE-HGF)POF2-331},
typ = {PUB:(DE-HGF)24},
url = {https://juser.fz-juelich.de/record/829370},
}