Objective: To identify patterns of striatal projection neurons (SPN) activities that code for akinetic and dyskinetic movement disorders in a mouse model of hemiparkinsonism and dyskinesia.

Background: L-DOPA is the reference treatment of Parkinson’s disease (PD). However, its chronic administration induces abnormal involuntary movements a condition termed L-DOPA-induced dyskinesia (LID). Among all the basal ganglia nuclei, the striatum is attributed a pivotal role in generating PD and LID. PD has been related to overactivity of the striatal projection neurons of the “indirect pathway” (iSPN) over the “direct pathway” striatal projections neurons (dSPN). Conversely, the phenomenology of LID has been broadly associated to a predominant role of dSPN over iSPN. However, the population dynamics of direct and indirect SPNs to the generation of these movement disorders is presently unknown.

Methods: Using in vivo calcium imaging we aimed to identify patterns of striatal SPN activities that code for akinetic and dyskinetic movement disorders in a mouse model of hemiparkinsonism and dyskinesia. We used D1-Cre and A2a-Cre transgenic mice to express the calcium indicator GCamP6f in dSPN and iSPN, respectively. Mice were implanted with accelerometer devices to record motor activity while imaging striatal activity in vivo in an open field. We measured motor and neural activity in intact and hemiparkinsonian mice at baseline and after administration of dopamine D1-agonist.

Results: Preliminary data show that calcium activity of direct and indirect SPNs increases with movement and during movement initiation in intact and hemiparkinsonian mice. We found a significant correlation between body acceleration and calcium signal activity. Interestingly, this correlation was lost after administration of D1-agonist. Differences in the number and the amplitude of calcium events were observed between intact and hemiparkinsonian mice in both striatal populations, before and after D1-agonist.

Conclusions: These preliminary results show that both striatal populations are modulated by movement in healthy and parkinsonian conditions, and that administration of D1-agonist alters the association between striatal neural activity and movement. Furthermore, dopamine depletion and D1-agonist treatment seem to change the nature of SPN calcium signals.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/spatiotemporal-patterns-of-direct-and-indirect-pathway-striatal-projection-neurons-in-mouse-model-of-parkinsons-disease-and-dyskinesia/