225 | AAV-mediated sparse labeling of striatal medium spiny neurons for analysis of dendritic spine density in a mouse model of Parkinson’s disease

Neural excitability, synaptic transmission and neuron-glia interactions

Author: Felix Fares Taie | Email: ffarestaie@fmed.uba.ar

Felix Fares Taie , Agostina Stahl , Veronica Risso , Irene Taravini , Lorena Rela

1° Universidad de Buenos Aires

The striatum is involved in action selection/initiation. It loses dopaminergic innervation in Parkinson’s disease as a result from mesencephalic dopaminergic neuron degeneration. Animal models show that dopaminergic denervation produces dendritic spine loss in striatal medium spiny neurons (MSNs) of both the direct (D1) and indirect (D2) pathways. In other disorders, dendritic spine loss has been linked to the dysfunction of microglia, immune cells with phagocytic capacity.
We hypothesize that reactive microglia in experimental parkinsonism participate in the pruning of striatal synaptic structures.
Here we characterized the time course of dopaminergic denervation of the striatum in a mouse model of experimental parkinsonism. We observed maximal dopaminergic denervation of the striatum 1 week post-lesion. To label MSNs, we administered a viral vector (AAV PHP.eB-pAAV-CAG-GFP) to reporter mice for D1 neurons (D1 Tom) with or without denervation that received doxycycline (a microglia inhibitor) or vehicle from 1 to 6 weeks post-lesion. We present an exploration of analysis parameters of micrographs acquired under structured illumination microscopy to determine dendritic spine density in MSNs in these groups to ultimately analyze correlation between spine density and behavior.
If the results support our hypothesis, it will contribute to position microglia-mediated processes as potential therapeutic targets to treat the disease.