Pallidal gap junctions-triggers of synchrony in Parkinson's disease?
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Pallidal gap junctions-triggers of synchrony in Parkinson's disease? / Schwab, Bettina C; Heida, Tjitske; Zhao, Yan; van Gils, Stephan A; van Wezel, Richard J A.
In: MOVEMENT DISORD, Vol. 29, No. 12, 10.2014, p. 1486-94.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Pallidal gap junctions-triggers of synchrony in Parkinson's disease?
AU - Schwab, Bettina C
AU - Heida, Tjitske
AU - Zhao, Yan
AU - van Gils, Stephan A
AU - van Wezel, Richard J A
N1 - © 2014 International Parkinson and Movement Disorder Society.
PY - 2014/10
Y1 - 2014/10
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.
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.
KW - Aged
KW - Aged, 80 and over
KW - Basal Ganglia/metabolism
KW - Computer Simulation
KW - Connexins/metabolism
KW - Female
KW - Gap Junctions/physiology
KW - Globus Pallidus/metabolism
KW - Glutamate Decarboxylase/metabolism
KW - Humans
KW - Male
KW - Microscopy, Confocal
KW - Models, Neurological
KW - Parkinson Disease/pathology
U2 - 10.1002/mds.25987
DO - 10.1002/mds.25987
M3 - SCORING: Journal article
C2 - 25124148
VL - 29
SP - 1486
EP - 1494
JO - MOVEMENT DISORD
JF - MOVEMENT DISORD
SN - 0885-3185
IS - 12
ER -