Pallidal gap junctions - Triggers of synchrony in Parkinson's disease?

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia. © 2014 International Parkinson and Movement Disorder Society
Original languageUndefined
Pages (from-to)1486-1494
Number of pages9
JournalMovement disorders
Volume29
Issue number12
DOIs
Publication statusPublished - 2014

Keywords

  • EWI-24973
  • BSS-Electrical Neurostimulation
  • oscillations
  • globus pallidus
  • METIS-305980
  • IR-91590
  • Connexin-36
  • Confocal Microscopy

Cite this

@article{7b7f901f285a410fa1dc6fc4369dddea,
title = "Pallidal gap junctions - Triggers of synchrony in Parkinson's disease?",
abstract = "Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50{\%} in the putamen, 43{\%} in the GPe, and 109{\%} in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia. {\circledC} 2014 International Parkinson and Movement Disorder Society",
keywords = "EWI-24973, BSS-Electrical Neurostimulation, oscillations, globus pallidus, METIS-305980, IR-91590, Connexin-36, Confocal Microscopy",
author = "B.C. Schwab and Tjitske Heida and Yan Zhao and {van Gils}, {Stephanus A.} and {van Wezel}, {Richard Jack Anton}",
note = "eemcs-eprint-24973",
year = "2014",
doi = "10.1002/mds.25987",
language = "Undefined",
volume = "29",
pages = "1486--1494",
journal = "Movement disorders",
issn = "0885-3185",
publisher = "Wiley",
number = "12",

}

Pallidal gap junctions - Triggers of synchrony in Parkinson's disease? / Schwab, B.C.; Heida, Tjitske; Zhao, Yan; van Gils, Stephanus A.; van Wezel, Richard Jack Anton.

In: Movement disorders, Vol. 29, No. 12, 2014, p. 1486-1494.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Pallidal gap junctions - Triggers of synchrony in Parkinson's disease?

AU - Schwab, B.C.

AU - Heida, Tjitske

AU - Zhao, Yan

AU - van Gils, Stephanus A.

AU - van Wezel, Richard Jack Anton

N1 - eemcs-eprint-24973

PY - 2014

Y1 - 2014

N2 - Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia. © 2014 International Parkinson and Movement Disorder Society

AB - Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia. © 2014 International Parkinson and Movement Disorder Society

KW - EWI-24973

KW - BSS-Electrical Neurostimulation

KW - oscillations

KW - globus pallidus

KW - METIS-305980

KW - IR-91590

KW - Connexin-36

KW - Confocal Microscopy

U2 - 10.1002/mds.25987

DO - 10.1002/mds.25987

M3 - Article

VL - 29

SP - 1486

EP - 1494

JO - Movement disorders

JF - Movement disorders

SN - 0885-3185

IS - 12

ER -