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• W4386816475 abstract "ABSTRACT Striatum, the input stage of the basal ganglia, is important for sensory-motor integration, initiation and selection of behaviour, 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 are altered. 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 glutamate drive to the SPNs would need to be altered to account for the activity level seen in SPNs during PD. In summary we find that the richness of the connectivity motifs is significantly decreased during PD, while at the same time a substantial enhancement of the effective glutamatergic drive to striatum is present. AUTHOR SUMMARY This in-silico study predicts that the impact the neuronal morphological alterations have on the striatal microcircuit connectivity. We find that the richness in the topological striatal motifs is significantly reduced in Parkinson’s disease, highlighting that just measuring the pairwise connectivity between neurons gives an incomplete description of network connectivity. Also we predict how the resulting electrophysiological changes of SPN excitability together with their reduced number of dendritic branches affect their response to the glutamate drive from cortex and thalamus. We find that the effective glutamatergic drive is likely significantly increased in PD, in accordance with the hyperglutamatergic hypothesis." @default.
• W4386816475 created "2023-09-18" @default.
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• W4386816475 date "2023-09-16" @default.
• W4386816475 modified "2023-10-02" @default.
• W4386816475 title "The impact of Parkinson's disease on striatal network connectivity and cortico-striatal drive: an in-silico study" @default.
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• W4386816475 doi "https://doi.org/10.1101/2023.09.15.557977" @default.
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