Using immunohistochemistry and confocal imaging, we reconstructed the distribution of Cx36, the major neural connexin, in human post-mortem tissue of the STN, GPe and GPi. Our preliminary analysis included tissue from 6 subjects (2x STN control, 2x STN PD, 1x GPi/e control, 1x GPi/e PD). Assuming that at least a part of the detected Cx36 indicates functional gap junctions, we implemented gap junctions in an existing computational model of the basal ganglia, the Rubin-Terman model including the STN, GPe and GPi.
Control tissue from the GPe/i showed punctuate Cx36 labeling, which was absent in a negative control leaving out the primary antibody. PD tissue additionally showed clusters of cells highly expressing Cx36. In the STN, only few spots of Cx36 were visible in control tissues. Their occurrence did not significantly increase in PD tissue. In the Rubin-Terman model (2002/2004) including STN, GPe and GPi, homogeneous gap junction coupling between nearest neighbors inside the GPe/i only slightly influenced the network behavior, unless the gap junction conductance was very high. However, clusters of cells in the GPi/e coupled via gap junctions led to bursting and synchronization, even if the gap junction conductance was comparably low.
Clusters of cells coupled via gap junctions seen in the GPi/e of the PD patient could explain the occurrence of bursting and synchronization in the basal ganglia. The modulation of gap junctions by dopamine might be a candidate for the remodeling of neural activity. Our experiments do not provide evidence for the functionality of the detected gap junctions.
|Conference||International Basal Ganglia Society Meeting 2013, Eilat, Israel|
|Period||1/01/13 → …|