The impact of Parkinson's disease on striatal network connectivity and corticostriatal drive: An in silico study.

Abstract

Striatum, the input stage of the basal ganglia, is important for sensory-motor integration, initiation and selection of behavior, as well as reward learning. Striatum receives glutamatergic inputs from mainly cortex and thalamus. In rodents, the striatal projection neurons (SPNs), giving rise to the direct and the indirect pathway (dSPNs and iSPNs, respectively), account for 95% of the neurons, and the remaining 5% are GABAergic and cholinergic interneurons. Interneuron axon terminals as well as local dSPN and iSPN axon collaterals form an intricate striatal network. Following chronic dopamine depletion as in Parkinson's disease (PD), both morphological and electrophysiological striatal neuronal features have been shown to be altered in rodent models. Our goal with this in silico study is twofold: (a) to predict and quantify how the intrastriatal network connectivity structure becomes altered as a consequence of the morphological changes reported at the single-neuron level and (b) to investigate how the effective glutamatergic drive to the SPNs would need to be altered to account for the activity level seen in SPNs during PD. In summary, we predict that the richness of the connectivity motifs in the striatal network is significantly decreased during PD while, at the same time, a substantial enhancement of the effective glutamatergic drive to striatum is present.