Pallidal gap junctions-triggers of synchrony in Parkinson's disease?
Bottom Line: 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 conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei.Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia.
Affiliation: Applied Analysis, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands; Biomedical Signals and Systems, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands.Show MeSH
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Mentions: Depending on their architecture and strength, GJs can be both synchronizing or desynchronizing40–42 and can interact in a nonlinear way with inhibitory synapses.43 Computational modeling can be used to study how a correlated input from cortex to STN affects synchronization, and how synchrony is spread to other nuclei. We implemented the network model proposed by Rubin and Terman,44 including 16 cells to represent each of STN, GPe, and GPi, using MATLAB.45 As shown in Figure 1A, the STN received excitatory input from the cortex, and both GPe and GPi received inhibitory input from the striatum. We added GJs between pairs of neurons inside the GPe and GPi. The neural dynamics in the GPe and GPi were thus governed by:2where Cm is the membrane capacity, V the transmembrane voltage, and Iionic, Isyn, IGJ, and Iapp the ionic, synaptic, GJ, and applied currents, respectively. GJs were modeled as ohmic resistors:3with GJ conductance gGJ. The ΔV represents the difference in transmembrane voltage between the connecting cells. We chose two different GJC architectures (Fig. 1B) to estimate the effect of newly synthesized GJ channels: (1) sparse coupling with an average of 0.5 GJs per cell and (2) numerous coupling with an average of 1 GJ per cell. To simulate dopamine modulation of the GJ strength, the GJ conductance in the GPe (gGPe) and GPi (gGPi) was varied between 0 and 0.25 mS/cm2, a realistic range for neural GJs46 but low compared with the conductances of chemical synapses. The STN received excitatory input from the cortex in the form of white noise, either completely correlated or completely uncorrelated. The inhibitory input from the striatum to the GPe and GPi was uncorrelated white noise. To quantify synchrony, we performed principal component analysis on spike activity as described in Lourens.47 In short, we calculated the number of principal components (PCs) needed to describe 95% of the information contained in the spike times for all 16 cells in each nucleus. High synchronization is associated with a small number of PCs, indicating that little variation is needed to describe the network state.
Affiliation: Applied Analysis, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands; Biomedical Signals and Systems, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands.