Pathophysiological signatures of functional connectomics in parkinsonian and dyskinetic striatal microcircuits

Abstract

A challenge in neuroscience is to integrate the cellular and system levels. For instance, we still do not know how a few dozen neurons organize their activity and relations in a microcircuit or module of histological scale. By using network theory and Ca2+ imaging with single-neuron resolution we studied the way in which striatal microcircuits of dozens of cells orchestrate their activity. In addition, control and diseased striatal tissues were compared in rats. In the control tissue, functional connectomics revealed small-world, scale-free and hierarchical network properties. These properties were lost during pathological conditions in ways that could be quantitatively analyzed. Decorticated striatal circuits disclosed that corticostriatal interactions depend on privileged connections with a set of highly connected neurons or “hubs”. In the 6-OHDA model of Parkinson's disease there was a decrease in hubs number; but the ones that remained were linked to dominant network states. l-DOPA induced dyskinesia provoked a loss in the hierarchical structure of the circuit. All these conditions conferred distinct temporal sequences to circuit activity. Temporal sequences appeared as particular signatures of disease process thus bringing the possibility of a future quantitative pathophysiology at a histological scale.

Keywords

• Striatal microcircuit
• Network properties
• Parkinsonian circuit
• Dyskinetic circuit
• l-DOPA